-
Alcaligenes Lipid A Functions as a Superior Mucosal Adjuvant to Monophosphoryl Lipid A via the Recruitment and Activation of CD11b+ Dendritic Cells in Nasal Tissue. Int. Immunol. (IF 4.4) Pub Date : 2023-11-25 Xiao Sun,Koji Hosomi,Atsushi Shimoyama,Ken Yoshii,Azusa Saika,Haruki Yamaura,Takahiro Nagatake,Hiroshi Kiyono,Koichi Fukase,Jun Kunisawa
We previously demonstrated that Alcaligenes-derived lipid A (ALA), which is produced from an intestinal lymphoid tissue-resident commensal bacterium, is an effective adjuvant for inducing antigen-specific immune responses. To understand the immunologic characteristics of ALA as a vaccine adjuvant, we here compared the adjuvant activity of ALA with that of a licensed adjuvant (monophosphoryl lipid A
-
IL-27 regulates NLRP3 inflammasome activation of MDSCs in experimental Sjögren's syndrome. Int. Immunol. (IF 4.4) Pub Date : 2023-11-07 Xiaoyu Xia,Qiqiang Long,Jie Zha,Tingting Jiang,Junqiao Guo,Bo Jiang,Xiaojing Li,Genhong Yao
Excessive NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation has an important function in the pathogenesis of Sjögren's syndrome (SS). Increased and dysfunctional myeloid-derived suppressor cells (MDSCs) promoted SS. However, NLRP3 inflammasome activation of MDSCs in SS and its regulated components are unclear. Splenic MDSCs were purified by immunomagnetic
-
Mucosal-associated invariant T cells from Clostridioides difficile-infected patients exhibit a distinct proinflammatory phenotype and enhanced cytotoxic activity. Int. Immunol. (IF 4.4) Pub Date : 2023-11-07 Steffen Brauns,Isabel Marquardt,Cosima Thon,Sarah Frentzel,Josefine Jakob,Jacqueline Färber,Lars Philipsen,Lothar Jänsch,Alexander Link,Dunja Bruder
Mucosal-associated invariant T (MAIT) cells are innate-like T cells mainly found in the mucosa and peripheral blood. We have recently demonstrated that Clostridioides difficile activates MAIT cells in vitro. However, their role in the pathogenesis of C. difficile infection (CDI) in human patients remains elusive to date. In this study, we performed comprehensive immunophenotyping of MAIT cells derived
-
Lung group 2 innate lymphoid cells differentially depend on local IL-7 for their distribution, activation, and maintenance in innate and adaptive immunity-mediated airway inflammation. Int. Immunol. (IF 4.4) Pub Date : 2023-11-07 Daichi Takami,Shinya Abe,Akihiro Shimba,Takuma Asahi,Guangwei Cui,Shizue Tani-Ichi,Takahiro Hara,Keishi Miyata,Masashi Ikutani,Kiyoshi Takatsu,Yuichi Oike,Koichi Ikuta
Interleukin-7 (IL-7) is a cytokine critical for the development and maintenance of group 2 innate lymphoid cells (ILC2s). ILC2s are resident in peripheral tissues such as the intestine and lung. However, whether IL-7 produced in the lung plays a role in the maintenance and function of lung ILC2s during airway inflammation remains unknown. IL-7 was expressed in bronchoalveolar epithelial cells and lymphatic
-
Identification of immune-related gene signatures for chronic obstructive pulmonary disease with metabolic syndrome: evidence from integrated bulk and single-cell RNA sequencing data. Int. Immunol. (IF 4.4) Pub Date : 2023-10-25 Yueren Wu,Mengyu Ma,Wenglam Choi,Weifang Xu,Jingcheng Dong
Chronic obstructive pulmonary disease (COPD) is closely related to innate and adaptive inflammatory immune responses. It is increasingly becoming evident that metabolic syndrome (MetS) affects a significant portion of COPD patients. Through this investigation, we identify shared immune-related candidate biological markers. The Weighted Gene Co-Expression Network Analysis (WGCNA) was utilized to reveal
-
Metabolic advantages of regulatory T cells dictated by cancer cells. Int. Immunol. (IF 4.4) Pub Date : 2023-10-14 Masaki Kondo,Shogo Kumagai,Hiroyoshi Nishikawa
Cancer cells employ glycolysis for their survival and growth (the 'Warburg effect'). Consequently, surrounding cells including immune cells in the tumor microenvironment (TME) are exposed to hypoglycemic, hypoxic, and low pH circumstances. Since effector T cells depend on the glycolysis for their survival and functions, the metabolically harsh TME established by cancer cells is unfavorable, resulting
-
The ligand interactions of B cell Siglecs are involved in the prevention of autoimmunity to sialylated self-antigens and in the quality control of signaling-competent B cells. Int. Immunol. (IF 4.4) Pub Date : 2023-10-06 Takeshi Tsubata
Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of membrane molecules that recognize sialic acid. Most of them are inhibitory receptors that inhibit immune-cell activation by recognizing sialic acid as a self-motif. Human B cells express CD22 (also known as Siglec-2), Siglec-5, Siglec-6 and Siglec-10 whereas mouse B cells express CD22 and Siglec-G (ortholog of human Siglec-10)
-
NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis. Int. Immunol. (IF 4.4) Pub Date : 2023-10-06 Susana López-López,María José Romero de Ávila,María Julia González-Gómez,María Luisa Nueda,Victoriano Baladrón,Eva M Monsalve,José Javier García-Ramírez,María José M Díaz-Guerra
IL-13 signaling polarizes macrophages to an M2 alternatively activated phenotype, which regulates tissue repair and anti-inflammatory responses. However, an excessive activation of this pathway leads to severe pathologies, such as allergic airway inflammation and asthma. In this work, we identified NOTCH4 receptor as an important modulator of M2 macrophage activation. We show that the expression of
-
Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function. Int. Immunol. (IF 4.4) Pub Date : 2023-10-06 Tian Qian,Bengang Huo,Xiaorong Deng,Xiaoli Song,Yiwei Jiang,Jurong Yang,Fei Hao
Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-κB signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome
-
Low-dose perinatal supplementation with Enterococcus faecalis increases concentrations of short-chain fatty acids in the offspring but does not protect against allergic asthma. Int. Immunol. (IF 4.4) Pub Date : 2023-10-06 Jeanne L Arntz,Moumen M Alhasan,Swarali Datye,Fariz G Kahhaleh,Yahia Almousa,Gabriela Barrientos,Andreas Schwiertz,Melanie L Conrad
Childhood allergic asthma is associated with a dysbiotic gut microbiome in early life, and maternal perinatal treatment with probiotics is a potential way alter the infant microbiome, which may improve asthma outcomes. This study used a mouse model to examine the effect of maternal supplementation with the probiotic Enterococcus faecalis on faecal short-chain fatty acid (SCFA) concentrations and asthma
-
Peripheral helper T cells, mavericks of peripheral immune responses. Int. Immunol. (IF 4.4) Pub Date : 2023-10-03 Hiroyuki Yoshitomi
Peripheral helper T (Tph) cells have been established, through intensive efforts to elucidate local immune responses in human rheumatoid arthritis (RA), as a CD4 subset intimately involved in acquired immunity in peripheral tissues. Initially, Tph cells were noted as a CD4 population that produces high levels of CXCL13 in RA synovial tissues, followed by a demonstration of their ability to help B cells
-
Cytokine signaling in chimeric antigen receptor T cell therapy. Int. Immunol. (IF 4.4) Pub Date : 2023-08-17 Yuki Kagoya
Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells can induce robust antitumor responses against hematologic malignancies. However, its efficacy is not durable in the majority of the patients, warranting further improvement of T cell functions. Cytokine signaling is one of the key cascades regulating T cell survival and effector functions. In addition to cytokines that
-
Follicular regulatory T cell subsets in mice and humans: origins, antigen specificity and function. Int. Immunol. (IF 4.4) Pub Date : 2023-08-07 Sophia Sokolova,Irina L Grigorova
Follicular regulatory T (Tfr) cells play various roles in immune responses, contributing to both positive and negative regulation of foreign-antigen-specific B cell responses, control over autoreactive antibody responses and autoimmunity, and B cell class-switching to IgE and allergy development. Studies conducted on mice uncovered various subsets of CXCR5 +FoxP3 +CD4 + Tfr cells that could differently
-
Contributions of the N-terminal flanking residues of an antigenic peptide from the Japanese cedar pollen allergen Cry j 1 to the T-cell activation by HLA-DP5. Int. Immunol. (IF 4.4) Pub Date : 2023-09-05 Seisuke Kusano,Sho Ueda,Daisuke Oryoji,Aya Toyoumi,Akiko Hashimoto-Tane,Hiroyuki Kishi,Hiroshi Hamana,Atsushi Muraguchi,Hui Jin,Hisashi Arase,Hiroko Miyadera,Reiko Kishikawa,Yasunobu Yoshikai,Hisakata Yamada,Ken Yamamoto,Yasuharu Nishimura,Takashi Saito,Takehiko Sasazuki,Shigeyuki Yokoyama
Cry j 1 is a major allergen present in Japanese cedar (Cryptomeria japonica) pollens. Peptides with the core sequence of KVTVAFNQF from Cry j 1 ('pCj1') bind to HLA-DP5 and activate Th2 cells. In this study, we noticed that Ser and Lys at positions -2 and -3, respectively, in the N-terminal flanking (NF) region to pCj1 are conserved well in HLA-DP5-binding allergen peptides. A competitive binding assay
-
Systemic immunometabolism and responses to vaccines: insights from T and B cell perspectives. Int. Immunol. (IF 4.4) Pub Date : 2023-06-18 Sam Nettelfield,Di Yu,Pablo F Cañete
Vaccination stands as the cornerstone in the battle against infectious diseases, and its efficacy hinges upon multifaceted host-related factors encompassing genetics, age, and metabolic status. Remarkably, suboptimal immune responses triggered by metabolic dysregulation is frequently observed in susceptible populations - ranging from malnourished individuals to the obese and elderly - pose a formidable
-
A CCR4 antagonist attenuates atopic dermatitis-like skin inflammation by inhibiting the recruitment and expansion of Th2 cells and Th17 cells. Int. Immunol. (IF 4.4) Pub Date : 2023-09-05 Masako Sato,Kazuhiko Matsuo,Yoko Susami,Ayaka Yamashita,Haruko Hayasaka,Yuta Hara,Keiji Nishiwaki,Naoki Oiso,Akira Kawada,Atsushi Otsuka,Takashi Nakayama
CCR4 is a major trafficking receptor for T-helper (Th) 2 cells and Th17 cells and is considered as a potential therapeutic target for atopic dermatitis (AD). The CCR4 ligands CCL17 and CCL22 have been reported to be upregulated in the skin lesions of AD patients. Of note, thymic stromal lymphopoietin (TSLP), a master regulator of the Th2 immune response, promotes the expression of CCL17 and CCL22 in
-
Foxp3 and Bcl6 deficiency synergistically induces spontaneous development of atopic dermatitis-like skin disease. Int. Immunol. (IF 4.4) Pub Date : 2023-09-05 Yuki Tai,Yuki Sakaida,Riyo Kawasaki,Kaori Kanemaru,Kazunori Akimoto,Frank Brombacher,Shuhei Ogawa,Yoshikazu Nakamura,Yohsuke Harada
Atopic dermatitis (AD) is a common chronic skin disease caused by immune dysfunction, specifically the hyperactivation of Th2 immunity. AD is a complex disease with multiple factors contributing to its development; however, the interaction between these factors is not fully understood. In this study, we demonstrated that the conditional deletion of both the forkhead box p3 (Foxp3) and B-cell lymphoma
-
Memory B cell differentiation from germinal centers. Int. Immunol. (IF 4.4) Pub Date : 2023-05-26 Takeshi Inoue
Establishment of humoral immune memory depends on two layers of defense: pre-existing antibodies secreted by long-lived plasma cells; and the antibodies produced by antigen-reactivated memory B cells. Memory B cells can now be considered as a second layer of defense upon re-infection by variant pathogens that have not been cleared by the long-lived plasma cell-mediated defense. Affinity-matured memory
-
Computer model of IL-6-dependent rheumatoid arthritis in F759 mice. Int. Immunol. (IF 4.4) Pub Date : 2023-09-05 Reiji Yamamoto,Satoshi Yamada,Toru Atsumi,Kaoru Murakami,Ari Hashimoto,Seiichiro Naito,Yuki Tanaka,Izuru Ohki,Yuta Shinohara,Norimasa Iwasaki,Akihiko Yoshimura,Jing-Jing Jiang,Daisuke Kamimura,Shintaro Hojyo,Shimpei I Kubota,Shigeru Hashimoto,Masaaki Murakami
The interleukin-6 (IL-6) amplifier, which describes the simultaneous activation of signal transducer and activator of transcription 3 (STAT3) and NF-κb nuclear factor kappa B (NF-κB), in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented
-
B cell-intrinsic DNase1L3 is essential for the T cell-independent type II response in mice. Int. Immunol. (IF 4.4) Pub Date : 2023-05-19 Kei Kato,Kei Haniuda,Saori Fukao,Daisuke Kitamura
T cell independent type II (TI-II) antigens, such as capsular polysaccharides, have multivalent epitopes, which induce B cell activation, plasma cell differentiation and antibody production by strongly cross-linking B cell receptors. However, the mechanism of B cell activation by TI-II antigens remains unclear. In this study, we demonstrate that DNA endonuclease DNase1L3 (also termed DNase γ) is required
-
Murine cytotoxic CD4+ T cells in the tumor microenvironment are at a hyper-maturation stage of Th1 CD4+ T cells sustained by IL-12. Int. Immunol. (IF 4.4) Pub Date : 2023-08-07 Yung-Chang Lin,Cheng-Heng Wu,Pin-Jung Chen,Chien-Hao Huang,Chan-Keng Yang,Avijit Dutta,Ching-Tai Huang,Chun-Yen Lin
The roles of tumor-infiltrating CD4+Foxp3- T cells are not well characterized due to their plasticity of differentiation, and varying levels of activation or exhaustion. To further clarify this issue, we used a model featuring subcutaneous murine colon cancer and analyzed the dynamic changes of phenotype and function of the tumor-associated CD4+ T-cell response. We found that, even at a late stage
-
An update on studies characterizing adaptive immune responses in SARS-CoV-2 infection and COVID-19 vaccination. Int. Immunol. (IF 4.4) Pub Date : 2023-08-07 Ricardo da Silva Antunes,Alba Grifoni,April Frazier,Daniela Weiskopf,Alessandro Sette
In this brief opinion piece, we highlight our studies characterizing adaptive SARS-CoV-2 immune responses in infection and vaccination, and the ability of SARS-CoV-2-specific T cells to recognize emerging variants of concern, and the role of pre-existing cross-reactive T cells. In the context of the debate on correlates of protection, the pandemic's progression in the past 3 years underlined the need
-
Subcutaneous immunisation with zymosan generates mucosal IgA-eliciting memory and protects mice from heterologous influenza virus infection. Int. Immunol. (IF 4.4) Pub Date : 2023-08-07 Yoshihito Nihei,Mizuki Higashiyama,Kosuke Miyauchi,Kei Haniuda,Yusuke Suzuki,Masato Kubo,Daisuke Kitamura
Immunoglobulin A (IgA) is the most abundant isotype of antibodies and provides a first line of defense at the mucosa against pathogens invading the host. It has been widely accepted that the mucosal IgA response provided by vaccination requires mucosal inoculation, and intranasal inoculation has been proposed for vaccines against influenza virus. Considering the difficulty of intranasal vaccination
-
Necessity of HuR/ELAVL1 for the activation-induced cytidine deaminase-dependent decrease in topoisomerase 1 in antibody diversification. Int. Immunol. (IF 4.4) Pub Date : 2023-08-07 Wajid Amin,Shoki Nishio,Tasuku Honjo,Maki Kobayashi
Activation-induced cytidine deaminase (AID)-dependent DNA cleavage is the initial event of antibody gene-diversification processes such as class switch recombination (CSR) and somatic hypermutation (SHM). We previously reported the requirement of an AID-dependent decrease of topoisomerase 1 (Top1) for efficient DNA cleavage, but the underlying molecular mechanism has remained elusive. This study focuses
-
Fibronectin on target cells attenuates natural cytotoxicity of NK cells via myeloid immune checkpoint ILT3/LILRB4/gp49B. Int. Immunol. (IF 4.4) Pub Date : 2023-07-07 Fumika Itagaki,Keita Nakatsuka,Haruka Sakai,Shota Endo,Mei-Tzu Su,Toshiyuki Takai
Natural killer (NK) cells play pivotal roles in innate immunity as well as in anti-tumor responses via natural killing, while their activity is tightly regulated by cell-surface inhibitory receptors. Immunoglobulin-like transcript 3/leukocyte immunoglobulin-like receptor B4 (ILT3/LILRB4, also known as gp49B in mice) is an inhibitory receptor expressed on activated NK cells as well as myeloid-lineage
-
Induction of allograft tolerance by adoptive transfer of donor B cells: an immune regulatory strategy for transplantation using MHC-matched iPS cells. Int. Immunol. (IF 4.4) Pub Date : 2023-07-07 Tomoki Murata,Ryo Otsuka,Airi Sasaki,Tomoki Kamatani,Haruka Wada,Hisashi Yamakawa,Yoshinori Hasegawa,Ken-Ichiro Seino
For cellular or tissue transplantation using induced pluripotent stem cells (iPSCs), from the viewpoint of time and economic cost, the use of allogeneic ones is being considered. Immune regulation is one of the key issues in successful allogeneic transplantation. To reduce the risk of rejection, several attempts have been reported to eliminate effects of the major histocompatibility complex (MHC) on
-
Zoobiquity experiments show the importance of the local MMP9-plasminogen axis in inflammatory bowel diseases in both dogs and patients. Int. Immunol. (IF 4.4) Pub Date : 2023-07-07 Takeshi Yamasaki,Noriyuki Nagata,Toru Atsumi,Rie Hasebe,Yuki Tanaka,Izuru Ohki,Shimpei Kubota,Yuta Shinohara,Yong Bin Teoh,Nozomu Yokoyama,Noboru Sasaki,Kensuke Nakamura,Hiroshi Ohta,Takehiko Katsurada,Yoshihiro Matsuno,Shintaro Hojyo,Shigeru Hashimoto,Mitsuyoshi Takiguchi,Masaaki Murakami
Using a zoobiquity concept, we directly connect animal phenotypes to a human disease mechanism: the reduction of local plasminogen levels caused by matrix metalloproteinase-9 (MMP9) activity is associated with the development of inflammation in the intestines of dogs and patients with inflammatory bowel disease. We first investigated inflammatory colorectal polyps (ICRPs), which are a canine gastrointestinal
-
Dupuytren's contracture-associated SNPs increase SFRP4 expression in non-immune cells including fibroblasts to enhance inflammation development. Int. Immunol. (IF 4.4) Pub Date : 2023-07-07 Hiroaki Kida,Jing-Jing Jiang,Yuichiro Matsui,Ikuko Takahashi,Rie Hasebe,Daisuke Kawamura,Takeshi Endo,Hiroki Shibayama,Makoto Kondo,Yasuhiko Nishio,Kinya Nishida,Yoshihiro Matsuno,Tsukasa Oikawa,Shimpei I Kubota,Shintaro Hojyo,Norimasa Iwasaki,Shigeru Hashimoto,Yuki Tanaka,Masaaki Murakami
Dupuytren's contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two single nucleotide polymorphisms
-
PCBP1 acts as a regulator of CCL2 expression in macrophages to induce recruitment of monocyte-derived macrophages into the inflamed colon. Int. Immunol. (IF 4.4) Pub Date : 2023-05-19 Xinquan Yang,Toshiki Yabe-Wada,Jia Han,Fumiji Saito,Chie Ogasawara,Sohsuke Yamada,Nobuyuki Onai
Intestinal macrophages with functional plasticity play essential roles in gut immune responses by increasing chemokines and cytokines, thereby contributing to the pathogenesis of inflammatory bowel disease (IBD). Poly(rC)-binding protein 1 (PCBP1), which is widely expressed in immune cells, binds to nucleic acids in mRNA processing, stabilization, translation and transcription. However, little is known
-
The role of the microbiota in myelopoiesis during homeostasis and inflammation. Int. Immunol. (IF 4.4) Pub Date : 2023-05-19 Yeji Kim,Nobuhiko Kamada
The microbiota engages in the development and maintenance of the host immune system. The microbiota affects not only mucosal tissues where it localizes but also the distal organs. Myeloid cells are essential for host defense as first responders of the host immune system. Their generation, called myelopoiesis, is regulated by environmental signals, including commensal microbiota. Hematopoietic stem
-
Immunogenicity evaluation of viral peptides via nonspecific interactions between anti-peptide IgYs and non-cognate peptides. Int. Immunol. (IF 4.4) Pub Date : 2023-05-08 Yuxi Zhou,Jingzhi Li,Wenya Wu,Yanfei Chen,Hu Cheng,Mengyu Li,Yiyue Sun,Jiao Yang,Daxin Peng,Qinghong Xue,Hongwei Ma
Immunogenicity can be evaluated by detecting antibodies (Abs) induced by an antigen. Presently deployed assays, however, do not consider the negative impacts of Ab poly-specificity, which is well established at the monoclonal antibody level. Here, we studied antibody poly-specificity at the serum level (i.e. nonspecific Ab-probe interactions, NSIs), and ended up establishing a new platform for viral
-
Exploring novel functions of BACH2 in the acquisition of antigen-specific antibodies. Int. Immunol. (IF 4.4) Pub Date : 2023-05-19 Kyoko Ochiai,Kazuhiko Igarashi
BACH2 [BTB (broad-complex, tramtrak and bric à brac) and CNC (cap 'n' collar) homolog 2] is known as a transcriptional repressor and broadly functions in regulating immune cell differentiation. Here, we focus on BACH2 function in B cells, where BACH2 was first shown to play an important role in the immune system. In B cells, BACH2 orchestrates the gene regulatory network that promotes class switch
-
Immune responses related to the immunogenicity and reactogenicity of COVID-19 mRNA vaccines. Int. Immunol. (IF 4.4) Pub Date : 2023-05-08 Takayuki Matsumura,Tomohiro Takano,Yoshimasa Takahashi
Vaccination for the prevention of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is considered the most promising approach to control the pandemic of coronavirus disease 2019 (COVID-19). Although various COVID-19 vaccines have been developed worldwide using several modalities, the vaccines that have shown the highest efficacy to date are mRNA vaccines. Despite their extensive
-
Repurposing crizotinib to target RIPK1-dependent cell death. Int. Immunol. (IF 4.4) Pub Date : 2023-05-08 Yajie Yu,Min Li,Shufang Fu,Xiaoyan He,Xinqian Hu,Guofeng Zhu,Jia Wang,Xiaoling You,Yan Mou,Zhi Ye,Jun Wei,Yunhong Zha
Receptor-interacting protein kinase 1 (RIPK1) has emerged as a key regulator of cell death and inflammation, which are implicated in the pathogenesis of many inflammatory and degenerative diseases. RIPK1 is therefore a putative therapeutic target in many of these diseases. However, no pharmacological inhibitor of RIPK1-mediated cell death is currently in clinical use. Recognizing that a repurposed
-
Roquin-dependent gene regulation in immune-mediated diseases and future therapies. Int. Immunol. (IF 4.4) Pub Date : 2023-04-04 Timsse Raj,Arlinda Negraschus,Vigo Heissmeyer
The RNA-binding proteins Roquin-1/2 and Regnase-1 exert essential regulation by controlling pro-inflammatory mRNA expression to prevent autoimmune disease. More recently, inhibition of this post-transcriptional gene regulatory program has been demonstrated to enable enhanced anti-tumor responses by tumor antigen-specific CD8+ T cells. In this review, we describe the functions of these RNA-binding proteins
-
Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS). Int. Immunol. (IF 4.4) Pub Date : 2023-04-04 Elliot Yi-Hsin Lin,Wen Xi,Nupur Aggarwal,Mari L Shinohara
Osteopontin (OPN) is a multifunctional protein, initially identified in osteosarcoma cells with its role of mediating osteoblast adhesion. Later studies revealed that OPN is associated with many inflammatory conditions caused by infections, allergic responses, autoimmunity and tissue damage. Many cell types in the peripheral immune system express OPN with various functions, which could be beneficial
-
Interferon regulatory factor-2 is required for the establishment of the gut intraepithelial T-cell compartment. Int. Immunol. (IF 4.4) Pub Date : 2023-05-08 Shigeo Tokumaru,Yuta Yamamoto,Kazuki Yoshizawa,Yuji Soejima,Hideki Sanjo,Shinsuke Taki
CD8αα+ intestinal intraepithelial lymphocytes (iIELs) are known for their unique role in keeping the integrity of the intestinal epithelial barrier, but factors affecting the development of these cells have not been thoroughly understood. Here, we found that the transcriptional regulator interferon regulatory factor-2 (IRF-2) plays a cell-intrinsic, indispensable role in establishing iIEL populations
-
Retinoic acid receptor activity is required for the maintenance of type 1 innate lymphoid cells. Int. Immunol. (IF 4.4) Pub Date : 2023-03-14 Takuma Asahi,Shinya Abe,Yuya Tajika,Hans-Reimer Rodewald,Veronika Sexl,Hiroshi Takeshima,Koichi Ikuta
Group 1 innate lymphoid cells (G1-ILCs) are innate immune effectors critical for the response to intracellular pathogens and tumors. G1-ILCs comprise circulating natural killer (NK) cells and tissue-resident type 1 ILCs (ILC1s). ILC1s mainly reside in barrier tissues and provide the initial sources of interferon-γ (IFN-γ) to prime the protecting responses against infections, which are followed by the
-
The RNA-editing enzyme ADAR1: a regulatory hub that tunes multiple dsRNA-sensing pathways. Int. Immunol. (IF 4.4) Pub Date : 2023-03-14 Taisuke Nakahama,Yukio Kawahara
Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-editing enzyme that catalyzes adenosine-to-inosine conversions in double-stranded RNAs (dsRNAs). In mammals, ADAR1 is composed of two isoforms: a nuclear short p110 isoform and a cytoplasmic long p150 isoform. Whereas both isoforms contain right-handed dsRNA-binding and deaminase domains, ADAR1 p150 harbors a Zα domain that binds to left-handed
-
Vaccination with the Omicron spike RBD boosts broadly neutralizing antibody levels and confers sustained protection even after acquiring immunity to the original antigen. Int. Immunol. (IF 4.4) Pub Date : 2023-04-04 Hitoshi Azuma,Yohei Kawano,Kiyomi Shitaoka,Takahiro Kawahara,Ayano Ito,Akifumi Higashiura,Yasuo Kitajima,Shun Ohki,Tomoharu Yasuda
The immune evasion of SARS-CoV-2 Omicron variants caused by multiple amino acid replacements in the receptor-binding domain (RBD) of the spike protein wanes the effectiveness of antibodies elicited by current SARS-CoV-2 booster vaccination. The vaccines that target Omicron strains have been recently developed, however, there has been a concern yet to be addressed regarding the negative aspect of the
-
The bZIP transcription factor BATF3/ZIP-10 suppresses innate immunity by attenuating PMK-1/p38 signaling. Int. Immunol. (IF 4.4) Pub Date : 2023-04-04 Muhammad Irfan Afridi,Zhongfan Zheng,Junqiang Liu,Lijuan Liu,Shan Zhang,Zhaozhong Zhu,Yousong Peng,Desheng Zhou,Haijun Tu
Innate immunity is the first line of host defense against pathogenic invasion in metazoans. The transcription factor basic leucine zipper transcriptional factor ATF-like 3 (BATF3) plays a crucial role in the development of conventional dendritic cells and the program of CD8 + T cell survival and memory, but the role of BATF3 in innate immune responses remains unclear. Here, we show an evolutionarily
-
The thin line between conventional dendritic cells (cDCs) and group 3 innate lymphoid cells (ILC3s) in the gut. Int. Immunol. (IF 4.4) Pub Date : 2023-03-14 Alina Ulezko Antonova,José Luís Fachi,Susan Gilfillan,Marco Colonna
Dendritic cells (DCs) express major histocompatibility complex class II (MHC-II) and are best known for proficiently presenting antigens to T cells, thereby eliciting specific adaptive T cell responses. Moreover, conventional DCs (cDCs) are specifically adept at handling intestinal antigens. Relatively recent discoveries and investigations have proven the existence of a new group of innate lymphocytes
-
Population dynamics and gene regulation of T cells in response to chronic antigen stimulation. Int. Immunol. (IF 4.4) Pub Date : 2023-02-11 Sunnie Hsiung,Takeshi Egawa
T cells are activated by antigen and co-stimulatory receptor signaling and undergo robust proliferation and differentiation into effector cells with protective function. Such quantitatively and qualitatively amplified T cell responses are effective in controlling acute infection and are followed by contraction of the effector population and the formation of resting memory T cells for enhanced protection
-
Fibronectin-LILRB4/gp49B interaction negatively regulates osteoclastogenesis through inhibition of RANKL-induced TRAF6/TAK1/NF-kB/MAPK signaling. Int. Immunol. (IF 4.4) Pub Date : 2023-03-14 Mei-Tzu Su,Karin Ono,Dai Kezuka,Shotaro Miyamoto,Yu Mori,Toshiyuki Takai
Dysregulation of osteoclasts, the multinucleated cells responsible for bone resorption, contributes to several degenerative bone disorders. Previously, we showed that blocking the leukocyte immunoglobulin (Ig)-like receptor B4 (LILRB4), a kind of inhibitory receptor that plays an important role in immune regulation, promotes osteoclast differentiation in vitro. Here, we explored whether gp49B, the
-
Maternal antibody repertoire restriction modulates the development of lupus-like disease in BXSB offspring. Int. Immunol. (IF 4.4) Pub Date : 2023-02-11 Jing Zhu,Samantha Naughton,Nina Bowman,Tanya LeRoith,Xin Luo,Caroline Leeth
Systemic lupus erythematosus (SLE) is a complex autoimmune disease that has a strong preference for women of child-bearing age. Maternal factors play an essential role in shaping the immune system of the newborn, yet it is unknown whether maternal factors could modulate the development of SLE in the offspring. Activation-induced cytidine deaminase (AID) is an enzyme required for somatic hypermutation
-
Activation of nucleotide-binding oligomerization domain 2 by muramyl dipeptide negatively regulates Toll-like receptor 9-mediated colonic inflammation through the induction of deubiquitinating enzyme A expression. Int. Immunol. (IF 4.4) Pub Date : 2023-02-11 Yasuhiro Masuta,Kosuke Minaga,Masayuki Kurimoto,Ikue Sekai,Akane Hara,Naoya Omaru,Natsuki Okai,Yasuo Otsuka,Ryutaro Takada,Tomoe Yoshikawa,Sho Masaki,Ken Kamata,Hajime Honjo,Yasuyuki Arai,Kouhei Yamashita,Masatoshi Kudo,Tomohiro Watanabe
Mutations in nucleotide-binding oligomerization domain 2 (NOD2) are associated with Crohn's disease (CD). Although NOD2 activation contributes to the maintenance of intestinal homeostasis through the negative regulation of pro-inflammatory cytokine responses mediated by Toll-like receptors (TLRs), the effects of NOD2 activation on interferon (IFN)-α responses induced by TLR9 have been poorly defined
-
Suppressive mechanisms of regulatory B cells in mice and humans. Int. Immunol. (IF 4.4) Pub Date : 2023-02-11 Yutaka Matsumura,Rei Watanabe,Manabu Fujimoto
B cells include immune-suppressive fractions, called regulatory B cells (Bregs), which regulate inflammation primarily through an interleukin 10 (IL-10)-mediated inhibitory mechanism. Several B-cell fractions have been reported as IL-10-producing Bregs in murine disease models and human inflammatory responses including autoimmune diseases, infectious diseases, cancer and organ-transplant rejection
-
Role of linear ubiquitination in inflammatory responses and tissue homeostasis. Int. Immunol. (IF 4.4) Pub Date : 2023-01-21 Katsuhiro Sasaki,Kazuhiro Iwai
Polyubiquitination is a post-translational modification involved in a wide range of immunological events, including inflammatory responses, immune cell differentiation, and development of inflammatory diseases. The versatile functions of polyubiquitination are based on different types of ubiquitin linkage, which enable various UBD (ubiquitin binding domain)-containing adaptor proteins to associate
-
Engagement with the TCR induces plasticity in antigenic ligands bound to MHC class I and CD1 molecules. Int. Immunol. (IF 4.4) Pub Date : 2023-01-21 Daisuke Morita,Minori Asa,Masahiko Sugita
Complementarity-determining regions (CDRs) of αβ T-cell receptors (TCRs) sense peptide-bound MHC (pMHC) complexes via chemical interactions, thereby mediating antigen specificity and MHC restriction. Flexible finger-like movement of CDR loops contributes to the establishment of optimal interactions with pMHCs. In contrast, peptide ligands captured in MHC molecules are considered more static because
-
Disruption of the intestinal barrier exacerbates experimental autoimmune pancreatitis by promoting the translocation of Staphylococcus sciuri into the pancreas. Int. Immunol. (IF 4.4) Pub Date : 2022-12-31 Tomoe Yoshikawa,Kosuke Minaga,Akane Hara,Ikue Sekai,Masayuki Kurimoto,Yasuhiro Masuta,Yasuo Otsuka,Ryutaro Takada,Ken Kamata,Ah-Mee Park,Shiki Takamura,Masatoshi Kudo,Tomohiro Watanabe
Autoimmune pancreatitis (AIP) and IgG4-related disease (IgG4-RD) are new disease entities characterized by enhanced IgG4 antibody responses and involvement of multiple organs, including the pancreas and salivary glands. Although the immunopathogenesis of AIP and IgG4-RD is poorly understood, we previously reported that intestinal dysbiosis mediates experimental AIP through the activation of IFN-α-
-
The proliferative activity levels of each immune cell population evaluated by mass cytometry are linked to the clinical phenotypes of systemic lupus erythematosus. Int. Immunol. (IF 4.4) Pub Date : 2023-01-21 Akiko Kajihara,Takayoshi Morita,Yasuhiro Kato,Hachiro Konaka,Teruaki Murakami,Yuta Yamaguchi,Shohei Koyama,Hyota Takamatsu,Masayuki Nishide,Yuichi Maeda,Akane Watanabe,Sumiyuki Nishida,Toru Hirano,Yoshihito Shima,Masashi Narazaki,Atsushi Kumanogoh
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, and many peripheral immune cell populations (ICPs) are thought to be altered according to the course of the disease. However, it is unclear which ICPs are associated with the clinical phenotypes of SLE. We analyzed peripheral blood mononuclear cells (PBMCs) of 28 SLE patients using mass cytometry and identified 30 ICPs. We determined
-
CCR4 plays a pivotal role in Th17 cell recruitment and expansion in a mouse model of rheumatoid arthritis. Int. Immunol. (IF 4.4) Pub Date : 2022-12-31 Tatsuma Honzawa,Kazuhiko Matsuo,Shunya Hosokawa,Mayu Kamimura,Yuichiro Kaibori,Yuta Hara,Daisuke Nagakubo,Naoki Oiso,Akira Kawada,Atsushi Otsuka,Osamu Yoshie,Takashi Nakayama
T helper 17 (Th17) cells express CC chemokine receptor 4 (CCR4) and secrete cytokines such as interleukin-17A (IL-17A) and granulocyte macrophage colony-stimulating factor (GM-CSF), while dendritic cells (DCs) produce CC chemokine ligand 22 (CCL22), a CCR4 ligand, upon stimulation with GM-CSF. Th17 cells are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA). CCL22 has also
-
CD8 T-cell heterogeneity during T-cell exhaustion and PD-1-targeted immunotherapy. Int. Immunol. (IF 4.4) Pub Date : 2022-10-05 Satomi Ando,Koichi Araki
Persistent antigenic stimulation results in loss of effector function or physical deletion of antigen-specific CD8 T cells. This T-cell state is called T-cell exhaustion and occurs during chronic infection and cancer. Antigen-specific CD8 T cells during T-cell exhaustion express the inhibitory receptor PD-1, the expression of which plays a major role in T-cell dysfunction. PD-1 blockade re-invigorates
-
The role of the microbiome in pancreatic oncogenesis. Int. Immunol. (IF 4.4) Pub Date : 2022-09-06 Donnele Daley
Bacterial dysbiosis is evolving as an advocate for carcinogenesis and has been associated with pancreatic cancer progression and survival outcomes. The gut and pancreas of cancer patients harbor a unique microbiome that differs significantly from that of healthy individuals. We believe that the pancreatic cancer microbiome regulates tumorigenesis by altering host cell function and modulating immune
-
A protein kinase D inhibitor suppresses AKT on T cells and antagonizes cancer immunotherapy by anti-PD-1. Int. Immunol. (IF 4.4) Pub Date : 2022-12-31 Kazuhide Miyamoto,Hodaka Hayabuchi,Yukiko Tokifuji,Makoto Ando,Nobuyuki Onishi,Tadashi Okamura,Akihiko Yoshimura,Shunsuke Chikuma
Antibodies that block the interaction between PD-1 and PD-1 ligands (anti-PD-1) are in clinical use for the treatment of cancer, yet their efficacy is limited. Pre-approved therapies that enhance the effect of anti-PD-1 in combination are beneficial. Small-molecule inhibitors that attenuate T cell receptor signaling are reported to prevent T cell exhaustion and induce memory T cells with stem cell
-
Neuroimmune crosstalk in the gut and liver. Int. Immunol. (IF 4.4) Pub Date : 2022-09-06 Toshiaki Teratani,Yohei Mikami,Takanori Kanai
It has long been assumed that the nervous system exerts distinct effects on immune functions, given the large number of immune disorders that are affected by mental stress. In fact, many different immune cells have been shown to possess a wide variety of neurotransmitter receptors and receive signals from various neurotransmitters, including acetylcholine and noradrenaline. Compared with the findings
-
Role of interferons (IFNs) in the differentiation of T peripheral helper (Tph) cells. Int. Immunol. (IF 4.4) Pub Date : 2022-09-09 Shuhei Tanemura,Noriyasu Seki,Hideto Tsujimoto,Shuntaro Saito,Jun Kikuchi,Kunio Sugahara,Keiko Yoshimoto,Katsuya Suzuki,Yuko Kaneko,Kenji Chiba,Tsutomu Takeuchi
Interleukin (IL)-21-producing T peripheral helper (Tph) cells are thought to contribute to extra-follicular B cell activation and play a pathogenic role in autoimmune diseases. In this study, we investigated the relationship between Tph cells and interferons (IFNs) in several autoimmune diseases because our previous study demonstrated that type I IFNs promote the differentiation of IL-21-producing
-
Immunogenicity, efficacy and safety of COVID-19 vaccines: an update of data published by 31 December 2021. Int. Immunol. (IF 4.4) Pub Date : 2022-12-31 Kun Xu,Chunxiang Fan,Yuxuan Han,Lianpan Dai,George F Gao
The unprecedented coronavirus disease 2019 (COVID-19) pandemic has caused a disaster for public health in the last 2 years, without any sign of an ending. Various vaccines were developed rapidly as soon as the outbreak occurred. Clinical trials demonstrated the reactogenicity, immunogenicity and protection efficacy in humans, and some of the vaccines have been approved for clinical use. However, waves
-
Nanaomycin E inhibits NLRP3 inflammasome activation by preventing mitochondrial dysfunction. Int. Immunol. (IF 4.4) Pub Date : 2022-09-09 Yudai Matsui,Naoki Takemura,Yoshitaka Shirasaki,Michihiro Takahama,Yoshihiko Noguchi,Kenta Ikoma,Yixi Pan,Shuhei Nishida,Manabu Taura,Akiyoshi Nakayama,Takashi Funatsu,Takuma Misawa,Yoshie Harada,Toshiaki Sunazuka,Tatsuya Saitoh
Nod-like receptor family pyrin domain-containing 3 (NLRP3) is a cytosolic innate immune receptor that senses organelle dysfunction induced by various stimuli, such as infectious, environmental, metabolic and drug stresses. Upon activation, NLRP3 forms an inflammasome with its adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, to trigger
-
Neutrophils in homeostasis and tissue repair. Int. Immunol. (IF 4.4) Pub Date : 2022-07-26 Hanjoo Brian Shim,Justin F Deniset,Paul Kubes
Neutrophils are the most abundant innate immune cell and are equipped with highly destructive molecular cargo. As such, these cells were long thought to be short-lived killer cells that unleash their full cytotoxic programs on pathogens following infection and on host bystander cells after sterile injury. However, this view of neutrophils is overly simplistic and as a result is outdated. Numerous studies