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Immuno-amnesia: Without B cells, T cells cannot remember. Sci. Immunol (IF 17.6) Pub Date : 2025-06-06 Jonathan S Maltzman
Why B cells are needed for optimal CD8 T cell memory.
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Inflammatory mischief managed: How retinoic acid calms heart attacks at the (marrow) source. Sci. Immunol (IF 17.6) Pub Date : 2025-06-06 Sahily Reyes-Esteves,Christopher A Hunter
Targeting vitamin A metabolism limits emergency hematopoiesis and promotes resolution of inflammation in myocardial infarction.
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Inducible protein degradation reveals inflammation-dependent function of the T reg cell lineage–defining transcription factor Foxp3 Sci. Immunol (IF 17.6) Pub Date : 2025-06-06 Christina Jäger, Polina Dimitrova, Qiong Sun, Jesse Tennebroek, Elisa Marchiori, Markus Jaritz, Rene Rauschmeier, Guillem Estivill, Anna Obenauf, Meinrad Busslinger, Joris van der Veeken
Regulatory T cells (T reg cells) are immunosuppressive CD4 T cells defined by expression of the transcription factor Foxp3. Genetic loss-of-function mutations in Foxp3 cause lethal multiorgan autoimmune inflammation resulting from defects in T reg cell development and suppressive activity. Whether T reg cells are continuously dependent on Foxp3 is still unclear. Here, we leveraged chemically induced
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An Il12 mRNA-LNP adjuvant enhances mRNA vaccine–induced CD8 T cell responses Sci. Immunol (IF 17.6) Pub Date : 2025-06-06 Emily A. Aunins, Anthony T. Phan, Mohamad-Gabriel Alameh, Garima Dwivedi, Elisa Cruz-Morales, David A. Christian, Ying Tam, Molly E. Bunkofske, Anabel Zabala Peñafiel, Keenan M. O’Dea, Maria Merolle, Colleen Furey, Phillip Scott, Robert H. Vonderheide, Scott E. Hensley, Ross M. Kedl, Drew Weissman, Christopher A. Hunter
Optimizing vaccine design to induce CD8 T cell responses has been challenging, but lipid nanoparticle (LNP)–encapsulated mRNA vaccines effectively generate CD8 T cell memory. Interleukin-12 (IL-12) supports CD8 T cell expansion and acquisition of effector function, but the role of IL-12 in the generation of CD8 T responses to mRNA vaccination is unclear. Here, we determine that endogenous IL-12 is
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Dissection of the immune landscape in psoriatic arthritis defines immunoproteasome up-regulation in treatment resistance Sci. Immunol (IF 17.6) Pub Date : 2025-06-06 Reut Tzemach, Chamutal Gur, Truong San Phan, Eyal David, Mor Zada, Merav D. Shmueli, Kfir Mazuz, Fadi Sheban, Anna Kurilovich, Maya Ben Yehuda, Victoria Furer, Ari Polachek, Smadar Gertel, Nimrod Snir, Tali Eviatar, Sharon Nevo, Yifat Merbl, Daphna Paran, Shuang-Yin Wang, Ori Elkayam, Ido Amit
Despite substantial advancements in psoriatic arthritis (PsA) treatment modalities, a considerable proportion of patients continue to experience persistent joint inflammation, unresponsive to the armamentarium of disease-modifying antirheumatic drugs. Identifying previously unknown biomarkers and targets for refractory disease is urgently needed. Here, using single-cell RNA sequencing of synovial fluid
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An activating Stat1 mutant disrupts normal STAT4 innate lymphocyte programs during viral infection Sci. Immunol (IF 17.6) Pub Date : 2025-05-30 Rachael L. Philips, Yi-Chu Liao, Colleen M. Lau, Tasha A. Morrison, Kan Jiang, Amal Hutchinson, Justin Shayne, Chen Yao, Joseph C. Sun, Heather D. Hickman, Joshua D. Milner, Steve Holland, Yuka Kanno, Michail S. Lionakis, John J. O’Shea
Interferonopathies drive autoimmunity but can also impair host responses to pathogens, including viral infections. To better understand viral susceptibility of patients with STAT1 gain-of-function (GOF) mutations, we generated conditional knockin mouse models to elucidate disease mechanisms and relevance of different immune subsets. Virally infected Stat1 GOF mice exhibited impaired early IFN-γ production
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Human LY9 governs CD4 + T cell IFN-γ immunity to Mycobacterium tuberculosis Sci. Immunol (IF 17.6) Pub Date : 2025-05-30 Masato Ogishi, Julia Puchan, Rui Yang, Andrés Augusto Arias, Ji Eun Han, Tina Nguyen, Rebeca Gutiérrez-Cózar, Clément Conil, Yoann Seeleuthner, Darawan Rinchai, Peng Zhang, Khoren Ponsin, Matthieu Chaldebas, Yi Feng, Anna-Lena Neehus, Ottavia M. Delmonte, Taushif Khan, Nils Landegren, Daniel Eriksson, Jonathan Bohlen, Jessica N. Peel, Iris Fagniez, Simon J. Pelham, Wei-Te Lei, Maya Chrabieh, Candice
CD4 + T cells are indispensable for optimal immunity to Mycobacterium tuberculosis ( M.tb ), a pathogen that triggers tuberculosis (TB) in humans. M.tb -specific human CD4 + T cells are known to polarize toward an interferon-γ (IFN-γ)–producing, CCR4 − CCR6 + CXCR3 + T-bet + RORγT + T helper 1* cell (T H 1*cell) memory phenotype. We report that autosomal recessive deficiency of the human lymphocytic
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An engineered viral protein activates STAT5 to prevent T cell suppression Sci. Immunol (IF 17.6) Pub Date : 2025-05-23 Yating Zheng, Zehui Gu, Claire E. Shudde, Taylor L. Piper, Xinyu Wang, Grace A. Aleck, Jiajia Zhou, Dana King, Monica K. Chanda, Lilliana Trinch, Weiping Zou, Adam H. Courtney
T cell therapy efficacy can be compromised if cytokine-induced Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling is dysregulated or insufficient to sustain functionality. Here, we demonstrate that LCK kinase activity can be recruited to noncanonical protein substrates to directly activate targeted STAT proteins in T cells. STAT activation was accomplished by engineering
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A light-regulated circadian timer optimizes neutrophil bactericidal activity to boost daytime immunity Sci. Immunol (IF 17.6) Pub Date : 2025-05-23 Lucia Yi Du, Pramuk Keerthisinghe, Leah Rolland, Yih Jian Sung, Hannah Darroch, Tanja Linnerz, Elina Ashimbayeva, Matthew J. Grant, Purvi M. Kakadia, Annasuya Ramachandran, Alexander Tups, Herman P. Spaink, Stefan K. Bohlander, James Cheeseman, Philip S. Crosier, Jonathan W. Astin, Guy Warman, Christopher J. Hall
The immune response exhibits strong circadian rhythmicity, with enhanced bacterial clearance often synchronized with an organism’s active phase. Despite providing the bulk of cellular antibacterial defense, the neutrophil clockwork is poorly understood. Here, we used larval zebrafish to explore the role of clock genes in neutrophils during infection. Per2 was required in neutrophils for reactive oxygen
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ILC3s promote intestinal tuft cell hyperplasia and anthelmintic immunity through RANK signaling Sci. Immunol (IF 17.6) Pub Date : 2025-05-16 Hongkai Xu, Yibo Wang, Wenyan Wang, Yang-Xin Fu, Ju Qiu, Yan Shi, Lei Yuan, Chen Dong, Xiaoyu Hu, Ye-Guang Chen, Xiaohuan Guo
Helminth infections, particularly in developing countries, remain a notable health burden worldwide. Group 3 innate lymphoid cells (ILC3s) are enriched in the intestine and play a critical role in immunity against extracellular bacteria and fungi. However, whether ILC3s are involved in intestinal helminth infection is still unclear. Here, we report that helminth infection reprograms ILC3s, which, in
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Cross-regulation between the nervous system and type 2 immunity Sci. Immunol (IF 17.6) Pub Date : 2025-05-16 Nicholas M. Mroz, Pailin Chiaranunt, Anna V. Molofsky, Ari B. Molofsky
Interactions between the nervous and immune systems are critical to healthy physiology and are altered in many human diseases. Many of the major players in type 2 immune responses, including type 2 lymphocytes and cytokines, mast cells, and immunoglobulin E, have been implicated in neuronal function and behavior. Conversely, neurons in both the central and peripheral nervous systems can affect type
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C/EBPα activates Irf8 expression in myeloid progenitors at the +56-kb enhancer to initiate cDC1 development Sci. Immunol (IF 17.6) Pub Date : 2025-05-16 Jing Chen, Tian-Tian Liu, Feiya Ou, Ray A. Ohara, Suin Jo, Joshua Luke Postoak, Takeshi Egawa, Ryan B. Day, Theresa L. Murphy, Kenneth M. Murphy, Sunkyung Kim
Development of type 1 conventional dendritic cells (cDC1s) underlies the capacity to generate antiviral and antitumor immune responses. Here, we identify the basis for cDC1 development from its earliest progenitors, determining the hierarchy of several required transcription factors and uncovering a series of mandatory cis interactions between constituent enhancers within the Irf8 superenhancer. We
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Uptake of lipids from ascites drives NK cell metabolic dysfunction in ovarian cancer Sci. Immunol (IF 17.6) Pub Date : 2025-05-09 Karen Slattery, Cong-Hui Yao, Eimear Mylod, John Scanlan, Barry Scott, Joseph Patrick Crowley, Orla McGowan, Gavin McManus, Martin Brennan, Katie O’Brien, Kate Glennon, Edward Corry, Ann Treacy, Rafael J. Argüello, Clair M. Gardiner, Marcia C. Haigis, Donal J. Brennan, Lydia Lynch
High-grade serous ovarian cancer (HGSOC) remains an urgent unmet clinical need, with more than 70% of patients presenting with metastatic disease. Many patients develop large volumes of ascites, which promotes metastasis and is associated with poor therapeutic response and survival. Immunotherapy trials have shown limited success, highlighting the need to better understand HGSOC immunology. Here, we
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Chimeric autoantibody receptor T cells clonally eliminate B cells producing autoantibodies against IFN-γ Sci. Immunol (IF 17.6) Pub Date : 2025-05-09 Jhan-Jie Peng, Jing-Ya Ding, Yingxi Xu, Han-Po Shih, You-Ning Lin, Tsai-Yi Wu, Yu-Fang Lo, Chia-Chi Lo, Chu-Fu Yeh, Chen-Yen Kuo, Kun-Hua Tu, Shang-Yu Wang, Wei-Te Lei, Ting-Shu Wu, Huang-Shen Lin, Chen-Hsiang Lee, Wen-Chi Huang, Yi-Chun Chen, Yuag-Meng Liu, Zhi-Yuan Shi, Ya-Ting Chang, Ling-Shan Syue, Po-Lin Chen, Soon-Hian Teh, Chia-Huei Chou, Mao-Wang Ho, Chih-Yu Chi, Ping-Chih Ho, Cheng-Lung Ku
Neutralizing anti–interferon-γ (IFN-γ) autoantibodies (nAIGAs) impair IFN-γ–mediated immunity, predisposing patients with nAIGAs to infection by nontuberculous mycobacteria, Talaromyces marneffei , and other intracellular pathogens. Current clinical management relies on continuous antimicrobial therapy, with no treatment offering sustained benefits. Here, we developed human chimeric autoantibody receptor
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Tolerance requires diversity (of antigen presenting cells). Sci. Immunol (IF 17.6) Pub Date : 2025-05-02 Danielle R Jacobsen,Stephanie C Eisenbarth
Multiple APC subsets cooperate to induce regulatory T cells in the gut.
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Distinct type I and II interferon responses direct cortical and medullary thymic epithelial cell development Sci. Immunol (IF 17.6) Pub Date : 2025-05-02 Abdulvasey Mohammed, Wenqing Wang, Martin Arreola, Benjamin D. Solomon, Priscila F. Slepicka, Kelsea M. Hubka, Hanh Dan Nguyen, Zihao Zheng, Michael G. Chavez, Christine Y. Yeh, Doo Kyung Kim, Michael R. Ma, Elisabeth Martin, Li Li, Anca M. Pasca, Virginia D. Winn, Casey A. Gifford, Veronika R. Kedlian, Jong-Eun Park, Purvesh Khatri, Georg A. Hollander, Maria Grazia Roncarolo, Vittorio Sebastiano,
Advances in genomics have redefined our understanding of thymic epithelial heterogeneity and architecture, yet signals driving thymic epithelial differentiation remain incompletely understood. Here, we elucidated pathways instructing human thymic epithelial cell development in the context of other anterior foregut–derived organs. Activation of interferon response gene regulatory networks distinguished
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Apoptotic cells are not all created equal Sci. Immunol (IF 17.6) Pub Date : 2025-05-02 Amanda O. Wong, Kodi S. Ravichandran
After lung injury, uptake of apoptotic neutrophils, but not epithelial cells, by alveolar macrophages prioritizes tissue repair over bacterial clearance (see related Research Article by Better et al. ).
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Cell type–specific efferocytosis determines functional plasticity of alveolar macrophages Sci. Immunol (IF 17.6) Pub Date : 2025-05-02 Julian Better, Mohammad Estiri, Michael Wetstein, Learta Pervizaj-Oruqaj, Christina Malainou, Victoria Ogungbemi-Alt, Maximiliano Ruben Ferrero, Martin Langelage, Irina Kuznetsova, Ana Ivonne Vazquez-Armendariz, Lucas Kimmig, Oleg Pak, Siavash Mansouri, Rajkumar Savai, Jochen Wilhelm, Ioannis Alexopoulos, Natascha Sommer, Susanne Herold, Ulrich Matt
Resolution of lung injuries is vital to maintain gas exchange, but there is an increased risk of secondary bacterial infections during this stage. Alveolar macrophages (AMs) are crucial to clear bacteria and control the resolution of inflammation, but environmental cues that switch functional phenotypes of AMs remain incompletely understood. Here, we found that AMs lack the capacity to mount an effective
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How dengue defies dogma: An extrafollicular tale Sci. Immunol (IF 17.6) Pub Date : 2025-05-02 Jordan Polster, David R. Martinez
The acute humoral immune response in patients with severe dengue can be extrafollicular, driven by a unique subset of CD4 + T cells.
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Fibroblastic reticular cells form reactive myeloid cell niches in human lymph nodes Sci. Immunol (IF 17.6) Pub Date : 2025-05-02 Mechthild Lütge, Lisa Kurz, Yves Stanossek, Samuel Meili, Hung-Wei Cheng, Angelina De Martin, Joshua Brandstadter, Ivan Maillard, Mark D. Robinson, Sandro J. Stoeckli, Natalia B. Pikor, Lucas Onder, Burkhard Ludewig
Lymph nodes play a key role in maintaining fluid balance in homeostatic and inflamed tissues and provide fibroblastic niche environments for optimal immune cell positioning and interaction. Here, we used single-cell and spatial transcriptomic analyses in combination with high-resolution imaging to molecularly define and functionally characterize niche-forming cells that control inflammation-driven
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T–B cell cooperation in ectopic lymphoid follicles propagates CNS autoimmunity Sci. Immunol (IF 17.6) Pub Date : 2025-04-25 Anna Kolz, Clara de la Rosa, Isabel J. Syma, Sarah McGrath, Vladyslav Kavaka, Rosa Schmitz, Anna S. Thomann, Martin Kerschensteiner, Eduardo Beltran, Naoto Kawakami, Anneli Peters
Meningeal ectopic lymphoid follicle (eLF)–like structures have been described in multiple sclerosis, but their role in central nervous system (CNS) autoimmunity is unclear. Here, we used a T helper 17 (T H 17) adoptive transfer experimental autoimmune encephalomyelitis model featuring formation of eLFs. Single-cell RNA sequencing revealed that clusters of activated B cells and B1/marginal zone–like
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Clone tracking through repeated malaria identifies high-fidelity memory CD4 T cell responses Sci. Immunol (IF 17.6) Pub Date : 2025-04-25 Jason Nideffer, Florian Bach, Felistas Nankya, Kenneth Musinguzi, Šimon Borna, Michelle Mantilla, Maato Zedi, Aracely Garcia Romero, Chloe Gerungan, Nora Yang, Soyeon Kim, Kattria van der Ploeg, Kylie Camanag, Luis Lopez, Evelyn Nansubuga, Joaniter I. Nankabirwa, Emmanuel Arinaitwe, Potchara Boonrat, Steven Strubbe, Alma-Martina Cepika, Saki Takahashi, Grant Dorsey, Bryan Greenhouse, Isabel Rodriguez-Barraquer
Few studies have tracked human CD4 + T cell clones through repeated infections. We used longitudinal single-cell RNA and T cell receptor (TCR) tracking to study the functional stability and memory potential of CD4 + T cell clonotypes during repeated Plasmodium falciparum ( Pf ) infections in Ugandan children and adults. Nearly all clonotypes displayed a strong preference for one of seven CD4 + subsets
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Endothelial-driven TGFβ signaling supports lung interstitial macrophage development from monocytes Sci. Immunol (IF 17.6) Pub Date : 2025-04-18 Wen Peng, Domien Vanneste, David Bejarano, Joan Abinet, Margot Meunier, Coraline Radermecker, Fabienne Perin, Didier Cataldo, Fabrice Bureau, Andreas Schlitzer, Qiang Bai, Thomas Marichal
Lung interstitial macrophages (IMs) are monocyte-derived parenchymal macrophages whose tissue-supportive functions remain unclear. Despite progress in understanding lung IM diversity and transcriptional regulation, the signals driving their development from monocytes and their functional specification remain unknown. Here, we found that lung endothelial cell–derived Tgfβ1 triggered a core Tgfβ receptor–dependent
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CCR8 + decidual regulatory T cells maintain maternal-fetal immune tolerance during early pregnancy Sci. Immunol (IF 17.6) Pub Date : 2025-04-18 Zhuqing Li, Pinxin Si, Tingting Meng, Xiaoran Zhao, Chendi Zhu, Dunfang Zhang, Shutong Meng, Nianyu Li, Ran Liu, Tianxiang Ni, Junhao Yan, Hongchang Li, Ning Zhao, Chao Zhong, Yingying Qin, WanJun Chen, Zi-Jiang Chen, Xue Jiao
Regulatory T (T reg ) cells play a vital role in maintaining maternal immune tolerance to the semiallogeneic fetus during pregnancy. T reg cell population heterogeneity and tissue-specific functions in the human decidua remain largely unknown. Here, using single-cell transcriptomic and T cell receptor sequencing of human CD4 + T cells from first-trimester deciduae and matched peripheral blood of pregnant
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Bcl11a maintains hematopoietic stem cell function but accelerates inflammation-driven exhaustion during aging Sci. Immunol (IF 17.6) Pub Date : 2025-04-11 Jing Wang, Linlin Zhang, Xinyu Cui, Xiang Xu, Rui Guo, Kairui Li, Li Zhang, Bing Xu, Cizhong Jiang, Yong Yu
Preserving hematopoietic stem cell (HSC) functionality is essential for maintaining healthy blood and the immune system throughout life. HSC function declines with age; however, the underlying mechanisms are not fully understood. Using an inducible mosaic mouse model to overexpress the transcription factor Bcl11a in the hematopoietic compartment, we found that an aging-related increase in Bcl11a mitigated
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Foxo1 regulates intestinal tissue–resident memory CD8 T cell biology in an anatomic compartment– and context-specific manner Sci. Immunol (IF 17.6) Pub Date : 2025-04-11 Paul Hsu, Eunice J. Choi, William H. Wong, Yun Hsuan Lin, Sara A. Vandenburgh, Yi Chia Liu, Priscilla Yao, Cynthia S. Indralingam, Gene W. Yeo, Elina I. Zuniga, Ananda W. Goldrath, Wei Wang, John T. Chang
Tissue-resident memory CD8 T (T RM ) cells serve as a front-line defense against microbial pathogens in barrier and mucosal tissues. Accurately predicting the roles of tissue-specific transcription factors (TFs) that regulate T RM biology remains a challenge. Here, by applying integrated transcriptomic and epigenomic analyses, we have identified an unexpected role for forkhead box O1 (Foxo1), a TF
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Psychological stress increases skin infection through the action of TGFβ to suppress immune-acting fibroblasts Sci. Immunol (IF 17.6) Pub Date : 2025-04-11 Hung Chan, Fengwu Li, Tatsuya Dokoshi, Kellen J. Cavagnero, Qing Li, Yang Chen, Carlos Aguilera, Teruaki Nakatsuji, Edward Liu, Aaryan Indra, Daping Yang, Ottaviani Valentina, Tomofumi Numata, Brittany Crown, Henry Li, Kevin J. Williams, Isaac M. Chiu, Steven J. Bensinger, WanJun Chen, Richard L. Gallo
Infections after psychological stress are a major health care problem. Single-cell transcriptomics and lipidomic profiling in a mouse model of stress show that dermal fibroblasts undergoing adipogenesis have defective responses to Staphylococcus aureus skin infection. Adrenalectomy or adrenergic inhibition restores the fibroblast adipogenic response to S. aureus and enables mice to effectively resist
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Luck gone cold: A trifecta of B cell mutations associates with cryoglobulinemia. Sci. Immunol (IF 17.6) Pub Date : 2025-04-04 Kangzhi Chen,Kevin C O'Connor
Triple somatic mutations in autoreactive B cells contribute to virus-associated autoimmune disease.
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Skin damage signals mediate allergic sensitization to spatially unlinked antigen Sci. Immunol (IF 17.6) Pub Date : 2025-04-04 Daniel A. Waizman, Isabela Brown-Soler, Anjelica L. Martin, Yifan Ma, Kenneth Zhou, Kavita Israni-Winger, Cuiling Zhang, Ruslan Medzhitov, Pierre Launay, Michaël F. Michieletto, Jorge Henao-Mejia, Noah W. Palm, Joe Craft, Anna Eisenstein, Andrew Wang
Our current understanding of immunity to pathogens suggests that anatomic coupling of antigens with danger signals is a required feature for the formation of immune memory. However, in the context of pathogen-independent inflammation, the stringency of this anatomical coupling is unclear. Here, we demonstrate that multiple modes of skin injury were sufficient to induce a humoral response to antigens
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Eosinophil innate immune memory after bacterial skin infection promotes allergic lung inflammation Sci. Immunol (IF 17.6) Pub Date : 2025-04-04 Mariem Radhouani, Asma Farhat, Anna Hakobyan, Sophie Zahalka, Lisabeth Pimenov, Alina Fokina, Anastasiya Hladik, Karin Lakovits, Jessica Brösamlen, Vojtech Dvorak, Natalia Nunes, Andreas Zech, Marco Idzko, Thomas Krausgruber, Jörg Köhl, Ozge Uluckan, Jiri Kovarik, Kai Hoehlig, Axel Vater, Margret Eckhard, Andy Sombke, Nikolaus Fortelny, Jörg Menche, Sylvia Knapp, Philipp Starkl
Microbial exposure at barrier interfaces drives development and balance of the immune system, but the consequences of local infections for systemic immunity and secondary inflammation are unclear. Here, we show that skin exposure to the bacterium Staphylococcus aureus persistently shapes the immune system of mice with specific impact on progenitor and mature bone marrow neutrophil and eosinophil populations
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Brain sensing of metabolic state regulates circulating monocytes Sci. Immunol (IF 17.6) Pub Date : 2025-04-04 Joao Paulo Cavalcanti de Albuquerque, Jenna Hunter, Rita G. Domingues, Erika Harno, Amy A. Worth, Fabrizio Maria Liguori, Aurora D’Alessio, Gabriella Aviello, David Bechtold, Anne White, Simon M. Luckman, Matthew R. Hepworth, Giuseppe D’Agostino
Changes in energy availability alter the dynamics of circulating immune cells. The existing view is that these effects are due to altered nutrient levels affecting peripheral tissue metabolism. Here, using mice and genetic approaches to manipulate the activity of distinct molecularly defined neurons, we show that the brain’s perception of hunger and satiety alone is sufficient to drive these immune
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An aging bone marrow exacerbates lung fibrosis by fueling profibrotic macrophage persistence Sci. Immunol (IF 17.6) Pub Date : 2025-03-28 Asma Farhat, Mariem Radhouani, Florian Deckert, Sophie Zahalka, Lisabeth Pimenov, Alina Fokina, Anna Hakobyan, Felicitas Oberndorfer, Jessica Brösamlen, Anastasiya Hladik, Karin Lakovits, Fanzhe Meng, Federica Quattrone, Louis Boon, Cornelia Vesely, Philipp Starkl, Nicole Boucheron, Jörg Menche, Joris van der Veeken, Wilfried Ellmeier, Anna-Dorothea Gorki, Clarissa Campbell, Riem Gawish, Sylvia Knapp
Pulmonary fibrosis is an incurable disease that manifests with advanced age. Yet, how hematopoietic aging influences immune responses and fibrosis progression remains unclear. Using heterochronic bone marrow transplant mouse models, we found that an aged bone marrow exacerbates lung fibrosis irrespective of lung tissue age. Upon lung injury, there was an increased accumulation of monocyte-derived alveolar
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Immunogenomic cancer evolution: A framework to understand cancer immunosuppression Sci. Immunol (IF 17.6) Pub Date : 2025-03-28 Shogo Kumagai, Yusaku Momoi, Hiroyoshi Nishikawa
The process of tumor development involves tumor cells eluding detection and suppression of immune responses, which can cause decreased tumor cell antigenicity, expression of immunosuppressive molecules, and immunosuppressive cell recruitment to the tumor microenvironment (TME). Immunologically and genomically integrated analysis (immunogenomic analysis) of patient specimens has revealed that oncogenic
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GM-CSF–mediated epithelial-immune cell cross-talk orchestrates pulmonary immunity to Aspergillus fumigatus Sci. Immunol (IF 17.6) Pub Date : 2025-03-21 Kathleen A. M. Mills, Frederike Westermann, Vanessa Espinosa, Eric Rosiek, Jigar V. Desai, Mariano A. Aufiero, Yahui Guo, Fitty L. Liu, Kennedy A. Mitchell, Selma Tuzlak, Donatella De Feo, Michail S. Lionakis, Amariliz Rivera, Burkhard Becher, Tobias M. Hohl
Aspergillus fumigatus causes life-threatening mold pneumonia in immunocompromised patients, particularly in those with quantitative or qualitative defects in neutrophils. Whereas innate immune cell cross-talk licenses neutrophil antifungal activity in the lung, the role of epithelial cells in this process is unknown. Here, we find that surfactant protein C (SPC)–expressing lung epithelial cells integrate
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Dysregulation of γδ intraepithelial lymphocytes precedes Crohn’s disease–like ileitis Sci. Immunol (IF 17.6) Pub Date : 2025-03-21 Weili Xu, Natasha B. Golovchenko, Irving U. Martínez-Vargas, Andrew Fong, Prateeksha Rout, Sajan Achi, Edie B. Bucar, Jonathan J. Hsieh, Kaylynn J. Vidmar, Lanjing Zhang, Alexandros D. Polydorides, Immo Prinz, George Kollias, Mark R. Frey, Theresa T. Pizarro, Michael P. Verzi, Karen L. Edelblum
Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) provide immunosurveillance of the intestinal barrier but are reduced in patients with active Crohn’s disease (CD). Here, we report an underappreciated role for γδ IELs in maintaining immunological tolerance during the onset and progression of CD-like ileitis using TNF ΔARE/+ mice. We found that TNF-induced down-regulation of epithelial
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DNMT1 inhibition reprograms T cells to NK-like cells with potent antitumor activity Sci. Immunol (IF 17.6) Pub Date : 2025-03-21 Yao Li, Jiongliang Wang, Linfu Zhou, Wenbin Gu, Le Qin, Dongdong Peng, Shanglin Li, Diwei Zheng, Qiting Wu, Youguo Long, Yao Yao, Shouheng Lin, Mingwei Sun, Xiaofei Zhang, Jie Wang, Pentao Liu, Xiangqian Kong, Peng Li
Inactivation of the transcription factor BCL11B reprograms T cells into induced-T-to-NK cells (ITNKs). However, it remains unclear how BCL11B suppresses natural killer (NK) cell transcriptional programs. Here, we identified that the DNA methyltransferase DNMT1 physically interacts with BCL11B, increasing BCL11B stability and the fidelity of DNA methylation maintenance for NK cell–related genes, thereby
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ATF4 drives regulatory T cell functional specification in homeostasis and obesity Sci. Immunol (IF 17.6) Pub Date : 2025-03-14 Ke Wang, Andrea Farrell, Enchen Zhou, Houji Qin, Zixuan Zeng, Kailun Zhou, Karina Cunha e Rocha, Dinghong Zhang, Gaowei Wang, Amha Atakilit, Dean Sheppard, Li-Fan Lu, Chunyu Jin, Wei Ying
Regulatory T cells (T regs ) have diverse functional specification in homeostasis and disease. However, how liver T regs function and are transcriptionally regulated in obesity is not well understood. Here, we identified that effector T regs expressing activating transcription factor 4 (ATF4) were enriched in the livers of obese mice. ATF4 was critical for driving an effector T reg transcriptional
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QRICH1 mediates an intracellular checkpoint for CD8 + T cell activation via the CARD11 signalosome Sci. Immunol (IF 17.6) Pub Date : 2025-03-14 Nicole M. Carter, Wihib D. Hankore, Yong-Kang Yang, Chao Yang, Shelby M. Hutcherson, Wyatt Fales, Anushka Ghosh, Piyusha Mongia, Sophie Mackinnon, Anna Brennan, Robert D. Leone, Joel L. Pomerantz
Antigen receptor signaling pathways that control lymphocyte activation depend on signaling hubs and negative regulatory proteins to fine-tune signaling outputs to ensure host defense and avoid pathogenic responses. Caspase recruitment domain–containing protein 11 (CARD11) is a critical signaling scaffold that translates T cell receptor (TCR) triggering into the activation of nuclear factor κB (NF-κB)
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MBPeace treaty: How myelin self-peptides broker CNS tolerance. Sci. Immunol (IF 17.6) Pub Date : 2025-03-07 Isabelle Leo,Etienne Caron
Specific MBP-derived self-peptides promote immune tolerance in the CNS and induce an unconventional regulatory T cell response.
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Continuous expression of TOX safeguards exhausted CD8 T cell epigenetic fate Sci. Immunol (IF 17.6) Pub Date : 2025-03-07 Yinghui J. Huang, Shin Foong Ngiow, Amy E. Baxter, Sasikanth Manne, Simone L. Park, Jennifer E. Wu, Omar Khan, Josephine R. Giles, E. John Wherry
Although checkpoint blockade temporarily improves exhausted CD8 T (T ex ) cell function, the underlying T ex epigenetic landscape remains largely unchanged, preventing durable T ex “reinvigoration” in cancer and chronic infections. The transcription factor TOX initiates T ex epigenetic programming, yet it remains unclear whether TOX continually preserves T ex biology after T ex establishment. Here
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Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity Sci. Immunol (IF 17.6) Pub Date : 2025-03-07 Benjamin Klein, Mack B. Reynolds, Bin Xu, Mehrnaz Gharaee-Kermani, Yiqing Gao, Celine C. Berthier, Svenja Henning, Lam C. Tsoi, Shannon N. Loftus, Kelsey E. McNeely, Christine M. Goudsmit, Amanda M. Victory, Craig Dobry, Grace A. Hile, Feiyang Ma, Jessica L. Turnier, Johann E. Gudjonsson, Mary X. O’Riordan, J. Michelle Kahlenberg
Photosensitivity is observed in numerous autoimmune diseases and drives poor quality of life and disease flares. Elevated epidermal type I interferon (IFN) production primes for photosensitivity and enhanced inflammation, but the substrates that sustain and amplify this cycle remain undefined. We show that IFN-induced Z-DNA binding protein 1 (ZBP1) stabilizes ultraviolet (UV) B–induced cytosolic Z-DNA
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Trouble at the border: An invading gut bacterium can break tolerance to self-RNA Sci. Immunol (IF 17.6) Pub Date : 2025-03-07 Rachael A. Clark
Mouse anti-RNA antibodies triggered by gut E. gallinarum correlate with self-RNA autoantibodies and lupus severity in humans.
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Dynamic STING repression orchestrates immune cell development and function Sci. Immunol (IF 17.6) Pub Date : 2025-03-07 Kennady Knox, Devon Jeltema, Nicole Dobbs, Kun Yang, Cong Xing, Kun Song, Zhen Tang, Gustavo Torres-Ramirez, Jiefu Wang, Shan Gao, Tuoqi Wu, Chen Yao, Jian Wang, Nan Yan
STING is an essential component of the innate immune system, yet homeostatic STING expression patterns and regulation are unknown. Using Sting1 IRES-EGFP reporter and conditional Sting1 transgenic mice, we found that regulation of STING expression is critical for immune cell development and functionality. STING expression was repressed in neutrophils, and forced STING expression or signaling drove
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Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy Sci. Immunol (IF 17.6) Pub Date : 2025-02-28 Vadim A. Klenchin, Natasha M. Clark, Nida K. Keles, Saverio Capuano, Rosemarie Mason, Guangping Gao, Aimee Broman, Emek Kose, Taina T. Immonen, Christine M. Fennessey, Brandon F. Keele, Jeffrey D. Lifson, Mario Roederer, Matthew R. Gardner, David T. Evans
An alternative to lifelong antiretroviral therapy (ART) is needed to achieve durable control of HIV-1. Here, we show that adeno-associated virus (AAV) delivery of two rhesus macaque antibodies to the simian immunodeficiency virus (SIV) envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected with barcoded SIV
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LCK–co-receptor association ensures T cell lineage fidelity and maximizes epitope-specific TCR diversity Sci. Immunol (IF 17.6) Pub Date : 2025-02-21 Justin B. Zhang, Priyanka Chaurasia, Angela Nguyen, Zijian Huang, Trang T. Nguyen, Hui Xu, Mai T. Tran, Hugh H. Reid, Claerwen M. Jones, Stefan A. Schattgen, Daniel Thiele, Paul G. Thomas, Jeanette Rientjes, Kim L. Good-Jacobson, Roland Ruscher, Dene R. Littler, Jamie Rossjohn, Pirooz Zareie, Nicole L. La Gruta
The interaction between the CD4/CD8 co-receptors and LCK (an Src family tyrosine kinase) is thought to augment T cell activation upon recognition of peptide-loaded major histocompatibility complexes (pMHCs). How this interaction influences antigen-specific T cell development is unclear however, as is its impact on naïve and immune antigen-specific T cell repertoires. In mice expressing mutated endogenous
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Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis Sci. Immunol (IF 17.6) Pub Date : 2025-02-21 Joona Sarkkinen, Dawit A. Yohannes, Nea Kreivi, Pia Dürnsteiner, Alexandra Elsakova, Jani Huuhtanen, Kirsten Nowlan, Goran Kurdo, Riikka Linden, Mika Saarela, Pentti J. Tienari, Eliisa Kekäläinen, Maria Perdomo, Sini M. Laakso
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection is a prerequisite for developing the disease. However, the pathogenic mechanisms that lead to MS remain to be determined. Here, we characterized the immune landscape of deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with MS (pwMS) using fine-needle aspirations
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TRAF3 is critical for initial T follicular helper cell specification via coordination of the IL-6R/IL-2R–BCL6 signaling nexus Sci. Immunol (IF 17.6) Pub Date : 2025-02-14 Peng Shao, Regina M. Antonetti, Tina Arkee, Emma L. Hornick, Hai Hui Xue, Gail A. Bishop, Noah S. Butler
CD4 + T follicular helper (T FH ) cells are essential for orchestrating robust humoral immunity, yet the signals that initiate T FH cell differentiation are not fully understood. We identified that the adapter protein TRAF3 was required for T FH cell differentiation and function during systemic inflammatory infections. Loss of CD4 + T cell–intrinsic TRAF3 impaired chromatin remodeling and transcriptional
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Linking vaccine adjuvant mechanisms of action to function Sci. Immunol (IF 17.6) Pub Date : 2025-02-14 Elana Ben-Akiva, Asheley Chapman, Tianyang Mao, Darrell J. Irvine
Vaccines deliver an immunogen in a manner designed to safely provoke an immune response, leading to the generation of memory T and B cells and long-lived antibody-producing plasma cells. Adjuvants play a critical role in vaccines by controlling how the immune system is exposed to the immunogen and providing inflammatory cues that enable productive immune priming. However, mechanisms of action underlying
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Afraid of needles? Try lotion: Engineering skin commensals for vaccination. Sci. Immunol (IF 17.6) Pub Date : 2025-02-07 Daniel A Shapiro,Christopher A Hunter
Commensals induce germinal center-like structures in the skin that can be used for vaccination.
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Is one lymphocyte's brake another lymphocyte's gas? Sci. Immunol (IF 17.6) Pub Date : 2025-02-07 Thomas T Xu,Shiv Pillai
PD-1 contributes to memory B cell development and robust antibody responses through B cell extrinsic and intrinsic mechanisms.
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Molecular determinants of cross-strain influenza A virus recognition by αβ T cell receptors Sci. Immunol (IF 17.6) Pub Date : 2025-02-07 Sergio M. Quiñones-Parra, Stephanie Gras, Thi H. O. Nguyen, Carine Farenc, Christopher Szeto, Louise C. Rowntree, Priyanka Chaurasia, Sneha Sant, Adrianus C. M. Boon, Dhilshan Jayasinghe, Guus F. Rimmelzwaan, Jan Petersen, Peter C. Doherty, Adam P. Uldrich, Dene R. Littler, Jamie Rossjohn, Katherine Kedzierska
Cross-reactive αβ T cell receptors (TCRs) recognizing multiple peptide variants can provide effective control of rapidly evolving viruses yet remain understudied. By screening 12 naturally occurring influenza-derived HLA-B*35:01–restricted nucleoprotein (NP) 418–426 epitopes (B*35:01-NP 418 ) that emerged since 1918 within influenza A viruses, including 2024 A/H5N1 viruses, we identified functional
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Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma Sci. Immunol (IF 17.6) Pub Date : 2025-02-07 Raphael Lutz, Alexandra M. Poos, Llorenç Solé-Boldo, Lukas John, Johanna Wagner, Nina Prokoph, Marc A. Baertsch, Dominik Vonficht, Subarna Palit, Alexander Brobeil, Gunhild Mechtersheimer, Nina Hildenbrand, Stefan Hemmer, Simon Steiger, Sabrina Horn, Wojciech Pepke, David M. Spranz, Christoph Rehnitz, Pooja Sant, Jan-Philipp Mallm, Mirco J. Friedrich, Philipp Reichert, Stefanie Huhn, Andreas Trumpp
The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell and spatial multiomics analyses of bone marrow–confined
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IL-4 induces CD22 expression to restrain the effector program of virtual memory T cells Sci. Immunol (IF 17.6) Pub Date : 2025-02-07 Bin Yang, Ophélie Piedfort, Guillem Sanchez-Sanchez, Arnaud Lavergne, Meijiao Gong, Garrie Peng, Ariel Madrigal, Georgios Petrellis, Brunette Katsandegwaza, Lucia Rodriguez Rodriguez, Alexis Balthazar, Sarah J. Meyer, Gert Van Isterdael, Julie Van Duyse, Fabienne Andris, Qiang Bai, Thomas Marichal, Bénédicte Machiels, Lars Nitschke, Hamed S. Najafabadi, Irah L. King, David Vermijlen, Benjamin G. Dewals
Parasitic helminths induce the production of interleukin-4 (IL-4), which causes the expansion of virtual memory CD8 + T cells (T VM cells), a cell subset that contributes to the control of coinfection with intracellular pathogens. However, the mechanisms regulating IL-4–dependent T VM cell activation and expansion remain ill defined. Here, we used single-cell RNA sequencing of CD8 + T cells to identify
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Trogocytosis of chimeric antigen receptors between T cells is regulated by their transmembrane domains Sci. Immunol (IF 17.6) Pub Date : 2025-01-31 Stefano Barbera, Matthijs J. A. Schuiling, Nathaniel A. Sanjaya, Ilkka Pietilä, Tina Sarén, Magnus Essand, Anna Dimberg
Trogocytosis is an exchange of membrane-associated molecules between cells that can either halt or boost immune responses. However, the mechanism that regulates trogocytosis in T cells and its consequences are not yet clear. Here, we demonstrate that T cells can exchange chimeric antigen receptors (CARs) by trogocytosis, thereby arming recipient T cells with the capacity to respond to tumor antigens
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Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression Sci. Immunol (IF 17.6) Pub Date : 2025-01-31 Catarina Gago da Graça, Amania A. Sheikh, Dane M. Newman, Lifen Wen, Sining Li, Jian Shen, Yuqi Zhang, Sarah S. Gabriel, David Chisanga, Justine Seow, Annika Poch, Lisa Rausch, Minh-Hanh T. Nguyen, Jayendra Singh, Chun-Hsi Su, Leonie A. Cluse, Carlson Tsui, Thomas N. Burn, Simone L. Park, Bianca Von Scheidt, Laura K. Mackay, Ajithkumar Vasanthakumar, David Bending, Wei Shi, Weiguo Cui, Jan Schröder
Stem-like T cells are attractive immunotherapeutic targets in patients with cancer given their ability to proliferate and differentiate into effector progeny. Thus, identifying T cells with enhanced stemness and understanding their developmental requirements are of broad clinical and therapeutic interest. Here, we demonstrate that during acute infection, the transcriptional regulator inhibitor of DNA
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The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis Sci. Immunol (IF 17.6) Pub Date : 2025-01-28 Miguel Marin-Rodero, Elisa Cintado, Alec J. Walker, Teshika Jayewickreme, Felipe A. Pinho-Ribeiro, Quentin Richardson, Ruaidhrí Jackson, Isaac M. Chiu, Christophe Benoist, Beth Stevens, José Luís Trejo, Diane Mathis
Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on how meningeal immunocytes guard brain homeostasis in healthy individuals remains limited. This study highlights the heterogeneous, polyfunctional regulatory T cell (T reg ) compartment in the meninges.
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Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy Sci. Immunol (IF 17.6) Pub Date : 2025-01-24 Katie Maurer, Cameron Y. Park, Shouvik Mani, Mehdi Borji, Florian Raths, Kenneth H. Gouin, Livius Penter, Yinuo Jin, Jia Yi Zhang, Crystal Shin, James R. Brenner, Jackson Southard, Sachi Krishna, Wesley Lu, Haoxiang Lyu, Domenic Abbondanza, Chanell Mangum, Lars Rønn Olsen, Michael J. Lawson, Martin Fabani, Donna S. Neuberg, Pavan Bachireddy, Eli N. Glezer, Samouil L. Farhi, Shuqiang Li, Kenneth J.
Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based
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Human naïve B cells recognize prepandemic influenza virus hemagglutinins Sci. Immunol (IF 17.6) Pub Date : 2025-01-24 Jared Feldman, Ana Sofia Ferreira Ramos, Mya Vu, Daniel P. Maurer, Victoria C. Rosado, Daniel Lingwood, Goran Bajic, Aaron G. Schmidt
Understanding the naïve B cell repertoire and its specificity for potential zoonotic threats, such as the highly pathogenic avian influenza (HPAI) H5Nx viruses, may allow prediction of infection- or vaccine-specific responses. However, this naïve repertoire and the possibility to respond to emerging, prepandemic viruses are largely undetermined. Here, we profiled naïve B cell reactivity against a prototypical