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  • Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor Programming
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-05
    Kyle T. Mincham; Anya C. Jones; Marie Bodinier; Naomi M. Scott; Jean-Francois Lauzon-Joset; Philip A. Stumbles; Anthony Bosco; Patrick G. Holt; Deborah H. Strickland

    We recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series

    更新日期:2020-12-02
  • Skin Immunity to Dermatophytes: From Experimental Infection Models to Human Disease
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-03
    Verónica L. Burstein; Ignacio Beccacece; Lorena Guasconi; Cristian J. Mena; Laura Cervi; Laura S. Chiapello

    Dermatophytoses (ringworms) are among the most frequent skin infections and are a highly prevalent cause of human disease worldwide. Despite the incidence of these superficial mycoses in healthy people and the compelling evidence on chronic and deep infections in immunocompromised individuals, the mechanisms controlling dermatophyte invasion in the skin are scarcely known. In the last years, the association

    更新日期:2020-12-02
  • Tumor-Associated Neutrophils and Macrophages—Heterogenous but Not Chaotic
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Ling Wu; Xiang H.-F. Zhang

    Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) have been extensively studied. Their pleotropic roles were observed in multiple steps of tumor progression and metastasis, and sometimes appeared to be inconsistent across different studies. In this review, we collectively discussed many lines of evidence supporting the mutual influence between cancer cells and TAMs/TANs. We

    更新日期:2020-12-02
  • Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Junxian Yang; Zhiwei Wu; Quan Long; Jiaqi Huang; Tiantian Hong; Wang Liu; Jiangguo Lin

    Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific

    更新日期:2020-12-02
  • CD73+ Dendritic Cells in Cascading Th17 Responses of Experimental Autoimmune Uveitis-Induced Mice
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    MinHee K. Ko; Hui Shao; Henry J. Kaplan; Deming Sun

    Previous studies have shown that CD73 is pivotal in the conversion of pro-inflammatory adenosine triphosphate into anti-inflammatory adenosine and that immune cells of the same type that express different levels of CD73 are functionally distinct. In this study we show that adenosine enhances the Th17 promoting effect of dendritic cells (DCs), and DCs expressing CD73 critically augment Th17 responses

    更新日期:2020-12-02
  • Novel Therapeutic Approaches to Familial HLH (Emapalumab in FHL)
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-30
    Pietro Merli; Mattia Algeri; Stefania Gaspari; Franco Locatelli

    Primary Hemophagocytic lymphohistiocytosis (pHLH) is a rare, life-threatening, hyperinflammatory disorder, characterized by uncontrolled activation of the immune system. Mutations affecting several genes coding for proteins involved in the cytotoxicity machinery of both natural killer (NK) and T cells have been found to be responsible for the development of pHLH. So far, front-line treatment, established

    更新日期:2020-12-02
  • Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-28
    Alansana Darboe; Carolyn M. Nielsen; Asia-Sophia Wolf; Jacob Wildfire; Ebrima Danso; Bakary Sonko; Christian Bottomley; Sophie E. Moore; Eleanor M. Riley; Martin R. Goodier

    Innate lymphoid cell (ILC) lineages mirror those of CD4+ T helper cell subsets, producing type 1, 2 and 3 cytokines respectively. Studies in adult human populations have shown contributions of non-cytotoxic ILC to immune regulation or pathogenesis in a wide range of diseases and have prompted investigations of potential functional redundancy between ILC and T helper cell compartments in neonates and

    更新日期:2020-12-02
  • Improved Anti-Inflammatory Effects of Liposomal Astaxanthin on a Phthalic Anhydride-Induced Atopic Dermatitis Model
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-04
    Yong Sun Lee; Seong Hee Jeon; Hyeon Joo Ham; Hee Pom Lee; Min Jong Song; Jin Tae Hong

    Previously, we found that astaxanthin (AST) elicited an anti-inflammatory response in an experimental atopic dermatitis (AD) model. However, the use of AST was limited because of low bioavailability and solubility. We hypothesized that liposome formulation of AST could improve this. In this study, we compared the anti-inflammatory and anti-dermatotic effects of liposomal AST (L-AST) and free AST. We

    更新日期:2020-12-01
  • The Roles of Tenascins in Cardiovascular, Inflammatory, and Heritable Connective Tissue Diseases
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-03
    Ken-ichi Matsumoto; Hiroki Aoki

    Tenascins are a family of multifunctional extracellular matrix (ECM) glycoproteins with time- and tissue specific expression patterns during development, tissue homeostasis, and diseases. There are four family members (tenascin-C, -R, -X, -W) in vertebrates. Among them, tenascin-X (TNX) and tenascin-C (TNC) play important roles in human pathologies. TNX is expressed widely in loose connective tissues

    更新日期:2020-12-01
  • Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-03
    Alfred D. Doyle; Mia Y. Masuda; Hirohito Kita; Benjamin L. Wright

    Eosinophilic esophagitis (EoE) is an antigen-driven disease associated with epithelial barrier dysfunction and chronic type 2 inflammation. Eosinophils are the defining feature of EoE histopathology but relatively little is known about their role in disease onset and progression. Classically defined as destructive, end-stage effector cells, eosinophils (a resident leukocyte in most of the GI tract)

    更新日期:2020-12-01
  • Lymphocyte Changes in Severe COVID-19: Delayed Over-Activation of STING?
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-03
    Jean-Marie Berthelot; Frédéric Lioté; Yves Maugars; Jean Sibilia

    Upon recognition of microbial DNA or self-DNA, the cyclic-GMP-AMP synthase (cGAS) of the host catalyzes the production of the cyclic dinucleotide cGAMP. cGAMP is the main activator of STING, stimulator of interferon genes, leading to interferon synthesis through the STING-TBK1-IRF3 pathway. STING is also a hub for activation of NF-κB and autophagy. The present review details the striking similarities

    更新日期:2020-12-01
  • Impact of Diabetes in Patients Diagnosed With COVID-19
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Mohamed Abu-Farha; Fahd Al-Mulla; Thangavel Alphonse Thanaraj; Sina Kavalakatt; Hamad Ali; Mohammed Abdul Ghani; Jehad Abubaker

    COVID-19 is a disease caused by the coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), known as a highly contagious disease, currently affecting more than 200 countries worldwide. The main feature of SARS-CoV-2 that distinguishes it from other viruses is the speed of transmission combined with higher risk of mortality from acute respiratory distress syndrome (ARDS). People with

    更新日期:2020-12-01
  • Antigen Specificity Enhances Disease Control by Tregs in Vitiligo
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-27
    Zhussipbek Mukhatayev; Emilia R. Dellacecca; Cormac Cosgrove; Rohan Shivde; Dinesh Jaishankar; Katherine Pontarolo-Maag; Jonathan M. Eby; Steven W. Henning; Yekaterina O. Ostapchuk; Kettil Cedercreutz; Alpamys Issanov; Shikhar Mehrotra; Andreas Overbeck; Richard P. Junghans; Joseph R. Leventhal; I. Caroline Le Poole

    Vitiligo is an autoimmune skin disease characterized by melanocyte destruction. Regulatory T cells (Tregs) are greatly reduced in vitiligo skin, and replenishing peripheral skin Tregs can provide protection against depigmentation. Ganglioside D3 (GD3) is overexpressed by perilesional epidermal cells, including melanocytes, which prompted us to generate GD3-reactive chimeric antigen receptor (CAR) Tregs

    更新日期:2020-12-01
  • Distinct Signatures in the Receptor Repertoire Discriminate CD56bright and CD56dim Natural Killer Cells
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-20
    Vera Schwane; Van Hung Huynh-Tran; Sarah Vollmers; Vivien Maria Yakup; Jürgen Sauter; Alexander H. Schmidt; Sven Peine; Marcus Altfeld; Laura Richert; Christian Körner

    NK cells are phenotypically and functionally diverse lymphocytes due to variegated expression of a large array of receptors. NK-cell activity is tightly regulated through integration of receptor-derived inhibitory and activating signals. Thus, the receptor profile of each NK cell ultimately determines its ability to sense aberrant cells and subsequently mediate anti-viral or anti-tumor responses. However

    更新日期:2020-12-01
  • B-Cell-Specific Myd88 L252P Expression Causes a Premalignant Gammopathy Resembling IgM MGUS
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-19
    Kristin Schmidt; Ulrike Sack; Robin Graf; Wiebke Winkler; Oliver Popp; Philipp Mertins; Thomas Sommermann; Christine Kocks; Klaus Rajewsky

    A highly recurrent somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-κB. It occurs in nearly all human patients with Waldenström’s macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here, we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation

    更新日期:2020-12-01
  • Identification of Mutated Peptides in Bladder Cancer From Exomic Sequencing Data Reveals Negative Correlation Between Mutation-Specific Immunoreactivity and Inflammation
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Chen Wang; Yu Ding; Yuanyong Liu; Qingchen Zhang; Shiqiang Xu; Liliang Xia; Huangqi Duan; Shujun Wang; Ping Ji; Weiren Huang; Guoping Zhao; Zhiwei Cao; Haibo Shen; Ying Wang

    Introduction and Objective Neoantigen-based immunotherapy is one of the breakthroughs in cancer immunotherapy. Benefit from the Cancer Genome Atlas database, we intended to identify mutant peptides with neoantigen property in bladder cancer (BC). Correlations between the immunoreactivity of candidate neoantigens and clinical manifestations were further analyzed. Methods HLA-A*02:01 restricted mutant

    更新日期:2020-12-01
  • The Intestinal Microbiota and Colorectal Cancer
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Yiwen Cheng; Zongxin Ling; Lanjuan Li

    The intestinal microbiota, composed of a large population of microorganisms, is often considered a “forgotten organ” in human health and diseases. Increasing evidence indicates that dysbiosis of the intestinal microbiota is closely related to colorectal cancer (CRC). The roles for intestinal microorganisms that initiated and facilitated the CRC process are becoming increasingly clear. Hypothesis models

    更新日期:2020-12-01
  • Metabolic Vulnerabilities and Epigenetic Dysregulation in Myeloproliferative Neoplasms
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Vasundhara Sharma; Kenneth L. Wright; Pearlie K. Epling-Burnette; Gary W. Reuther

    The Janus kinase 2 (JAK2)-driven myeloproliferative neoplasms (MPNs) are associated with clonal myelopoiesis, elevated risk of death due to thrombotic complications, and transformation to acute myeloid leukemia (AML). JAK2 inhibitors improve the quality of life for MPN patients, but these approved therapeutics do not readily reduce the natural course of disease or antagonize the neoplastic clone. An

    更新日期:2020-12-01
  • Molecular and Structural Basis of DNA Sensors in Antiviral Innate Immunity
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Ayesha Zahid; Hazrat Ismail; Bofeng Li; Tengchuan Jin

    DNA viruses are a source of great morbidity and mortality throughout the world by causing many diseases; thus, we need substantial knowledge regarding viral pathogenesis and the host’s antiviral immune responses to devise better preventive and therapeutic strategies. The innate immune system utilizes numerous germ-line encoded receptors called pattern-recognition receptors (PRRs) to detect various

    更新日期:2020-12-01
  • Systemic CD4 Immunity as a Key Contributor to PD-L1/PD-1 Blockade Immunotherapy Efficacy
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-30
    Miren Zuazo; Hugo Arasanz; Ana Bocanegra; Gonzalo Fernandez; Luisa Chocarro; Ruth Vera; Grazyna Kochan; David Escors

    PD-L1/PD-1 blockade immunotherapy has significantly improved treatment outcome for several cancer types compared to conventional cytotoxic therapies. However, the specific molecular and cellular mechanisms behind its efficacy are currently unclear. There is increasing evidence in murine models and in patients that unveil the key importance of systemic immunity to achieve clinical responses under several

    更新日期:2020-12-01
  • Treatment Progress of Immune Checkpoint Blockade Therapy for Glioblastoma
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-29
    Na Zhang; Li Wei; Meng Ye; Chunsheng Kang; Hua You

    Glioblastoma (GBM) is a highly malignant and aggressive primary brain tumor mostly prevalent in adults and is associated with a very poor prognosis. Moreover, only a few effective treatment regimens are available due to their rapid invasion of the brain parenchyma and resistance to conventional therapy. However, the fast development of cancer immunotherapy and the remarkable survival benefit from immunotherapy

    更新日期:2020-12-01
  • The cGAS-STING Pathway in Hematopoiesis and Its Physiopathological Significance
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-29
    Weinian Liao; Changhong Du; Junping Wang

    Cytosolic DNA sensing is a fundamental mechanism by which organisms handle various stresses, including infection and genotoxicity. The hematopoietic system is sensitive to stresses, and hematopoietic changes are often rapid and the first response to stresses. Based on the transcriptome database, cytosolic DNA sensing pathways are widely expressed in the hematopoietic system, and components of these

    更新日期:2020-12-01
  • Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-28
    Sara Andreone; Adriana Rosa Gambardella; Jacopo Mancini; Stefania Loffredo; Simone Marcella; Valentina La Sorsa; Gilda Varricchi; Giovanna Schiavoni; Fabrizio Mattei

    Interleukin-33 (IL-33) is an epithelial-derived cytokine that can be released upon tissue damage, stress, or infection, acting as an alarmin for the immune system. IL-33 has long been studied in the context of Th2-related immunopathologies, such as allergic diseases and parasitic infections. However, its capacity to stimulate also Th1-type of immune responses is now well established. IL-33 binds to

    更新日期:2020-12-01
  • Hypoxia Shapes Autophagy in LPS-Activated Dendritic Cells
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-28
    Sara Monaci; Carlo Aldinucci; Daniela Rossi; Gaia Giuntini; Irene Filippi; Cristina Ulivieri; Giuseppe Marotta; Silvano Sozzani; Fabio Carraro; Antonella Naldini

    During their lifespan, dendritic cells (DCs) are exposed to different pO2 levels that affect their differentiation and functions. Autophagy is one of the adaptive responses to hypoxia with important implications for cell survival. While the autophagic machinery in DCs was shown to impact signaling of TLRs, its regulation by the MD-2/TLR4 ligand LPS is still unclear. The aim of this study was to evaluate

    更新日期:2020-12-01
  • Innate Lymphoid Cells in Human Pregnancy
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-28
    João Mendes; Ana Luísa Areia; Paulo Rodrigues-Santos; Manuel Santos-Rosa; Anabela Mota-Pinto

    Innate lymphoid cells (ILCs) are a new set of cells considered to be a part of the innate immune system. ILCs are classified into five subsets (according to their transcription factors and cytokine profile) as natural killer cells (NK cells), group 1 ILCs, group 2 ILCs, group 3 ILCs, and lymphoid tissue inducers (LTi). Functionally, these cells resemble the T helper population but lack the expression

    更新日期:2020-12-01
  • MAIT Cells in Barrier Tissues: Lessons from Immediate Neighbors
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-26
    Ali Amini; Declan Pang; Carl-Philipp Hackstein; Paul Klenerman

    Mucosal-associated invariant T (MAIT) cells are innate-like T cells present at considerable frequencies in human blood and barrier tissues, armed with an expanding array of effector functions in response to homeostatic perturbations. Analogous to other barrier immune cells, their phenotype and function is driven by crosstalk with host and dynamic environmental factors, most pertinently the microbiome

    更新日期:2020-12-01
  • Current Progress on Host Antiviral Factor IFITMs
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-26
    Linzhu Ren; Shouwen Du; Wang Xu; Tiyuan Li; Shipin Wu; Ningyi Jin; Chang Li

    Host antiviral factor interferon-induced transmembrane proteins (IFITMs) are a kind of small-molecule transmembrane proteins induced by interferon. Their broad-spectrum antiviral activity and unique ability to inhibit viral invasion have made them a hot molecule in antiviral research in recent years. Since the first demonstration of their natural ability to resist viral infection in 1996, IFITMs have

    更新日期:2020-12-01
  • Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-26
    Yuanhao Chang; Guanzhang Li; You Zhai; Lijie Huang; Yuemei Feng; Di Wang; Wei Zhang; Huimin Hu

    Glutaredoxin is central to cellular redox chemistry and regulates redox homeostasis and malignant progression of many cancers. In glioma, the role of its coding gene (GLRX) remains unclear. We aimed to elucidate the role of glutaredoxin at the transcriptome level and its clinical prognostic value in glioma. In total, we evaluated 1,717 glioma samples with transcriptome data and corresponding clinical

    更新日期:2020-12-01
  • IGLR-2, a Leucine-Rich Repeat Domain Containing Protein, Is Required for the Host Defense in Caenorhabditis elegans
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-21
    Cheng-Ju Kuo; Ya-Chu Hsu; Sin-Tian Wang; Bang-Yu Liou; Serene Boon-Yuean Lim; Yi-Wei Chen; Chang-Shi Chen

    Enterohemorrhagic Escherichia coli (EHEC), a human pathogen, also infects Caenorhabditis elegans. We demonstrated previously that C. elegans activates the p38 MAPK innate immune pathway to defend against EHEC infection. However, whether a C. elegans pattern recognition receptor (PRR) exists to regulate the immune pathway remains unknown. PRRs identified in other metazoans contain several conserved

    更新日期:2020-12-01
  • Macrophages in Organ Transplantation
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-20
    Farideh Ordikhani; Venu Pothula; Rodrigo Sanchez-Tarjuelo; Stefan Jordan; Jordi Ochando

    Current immunosuppressive therapy has led to excellent short-term survival rates in organ transplantation. However, long-term graft survival rates are suboptimal, and a vast number of allografts are gradually lost in the clinic. An increasing number of animal and clinical studies have demonstrated that monocytes and macrophages play a pivotal role in graft rejection, as these mononuclear phagocytic

    更新日期:2020-12-01
  • PD-L1-Mediated Immunosuppression in Glioblastoma Is Associated With the Infiltration and M2-Polarization of Tumor-Associated Macrophages
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-20
    Zhiyuan Zhu; Hongbo Zhang; Baodong Chen; Xing Liu; Shizhong Zhang; Zhitao Zong; Mengqi Gao

    There has been no significant improvements for immune checkpoint inhibitors since its first use. Tumour-associated macrophages (TAMs) are critical mediators in the PD-1/PD-L1 axis, contributing to the immunosuppressive tumour microenvironment. This study aims to investigate the potential role of PD-L1 in regulating TAMs in glioblastoma. Gene expression data and clinical information of glioma patients

    更新日期:2020-12-01
  • Enhanced Fatty Acid Synthesis Leads to Subset Imbalance and IFN-γ Overproduction in T Helper 1 Cells
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-20
    Shigeru Iwata; Mingzeng Zhang; He Hao; Gulzhan Trimova; Maiko Hajime; Yusuke Miyazaki; Naoaki Ohkubo; Yurie Satoh Kanda; Yasuyuki Todoroki; Hiroko Miyata; Masanobu Ueno; Atsushi Nagayasu; Shingo Nakayamada; Kei Sakata; Yoshiya Tanaka

    Recent reports have shown the importance of IFN-γ and T-bet+ B cells in the pathology of SLE, suggesting the involvement of IFN-γ-producing T-bet+ CD4+ cells, i.e., Th1 cells. This study determined the changes in Th1 subsets with metabolic shift and their potential as therapeutic targets in SLE. Compared with healthy donors, patients with SLE had higher numbers of T-bethiCXCR3lo effector cells and

    更新日期:2020-12-01
  • Optimized Protocol for Characterization of Mouse Gut Innate Lymphoid Cells
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-19
    Ana Valle-Noguera; María José Gómez-Sánchez; Mathilde J. H. Girard-Madoux; Aranzazu Cruz-Adalia

    Since their discovery, innate lymphoid cells (ILCs) have gradually been gaining greater relevance in the field of immunology due to their multiple functions in the innate immune response. They can mainly be found in mucosal and barrier organs like skin, gut, and lungs, and have been classified into five main types (NKs, ILC1s, ILC2s, ILC3s, and Lti cells) according to their function and development

    更新日期:2020-12-01
  • Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-15
    Casey P. Shannon; Travis M. Blimkie; Rym Ben-Othman; Nicole Gladish; Nelly Amenyogbe; Sibyl Drissler; Rachel D. Edgar; Queenie Chan; Mel Krajden; Leonard J. Foster; Michael S. Kobor; William W. Mohn; Ryan R. Brinkman; Kim-Anh Le Cao; Richard H. Scheuermann; Scott J. Tebbutt; Robert E.W. Hancock; Wayne C. Koff; Tobias R. Kollmann; Manish Sadarangani; Amy Huei-Yi Lee

    Background Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. Methods We applied cutting edge multi-omics approaches to extensively characterize temporal molecular

    更新日期:2020-12-01
  • Differential Immune Response to Infection and Acute Inflammation Along the Epididymis
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-03
    Christiane Pleuger; Erick José Ramo Silva; Adrian Pilatz; Sudhanshu Bhushan; Andreas Meinhardt

    The epididymis is a tubular structure connecting the vas deferens to the testis. This organ consists of three main regions—caput, corpus, and cauda—that face opposing immunological tasks. A means of combating invading pathogens is required in the distally located cauda, where there is a risk of ascending bacterial infections originating from the urethra. Meanwhile, immune tolerance is necessary at

    更新日期:2020-11-27
  • Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Elena Blanco; Natalia Izotova; Claire Booth; Adrian James Thrasher

    X-linked severe immunodeficiency disease (SCID-X1) is an inherited, rare, and life-threating disease. The genetic origin is a defect in the interleukin 2 receptor γ chain (IL2RG) gene and patients are classically characterized by absence of T and NK cells, as well as presence of partially-functional B cells. Without any treatment the disease is usually lethal during the first year of life. The treatment

    更新日期:2020-11-27
  • Glioblastoma Immunotherapy Targeting the Innate Immune Checkpoint CD47-SIRPα Axis
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Jinyang Hu; Qungen Xiao; Minhai Dong; Dongsheng Guo; Xudong Wu; Baofeng Wang

    Glioblastoma Multiforme (GBM) is the most common and aggressive form of intracranial tumors with poor prognosis. In recent years, tumor immunotherapy has been an attractive strategy for a variety of tumors. Currently, most immunotherapies take advantage of the adaptive anti-tumor immunity, such as cytotoxic T cells. However, the predominant accumulation of tumor-associated microglia/macrophages (TAMs)

    更新日期:2020-11-27
  • Immune Checkpoint Targeted Therapy in Glioma: Status and Hopes
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-29
    Yangzhi Qi; Baohui Liu; Qian Sun; Xiaoxing Xiong; Qianxue Chen

    Glioma is the most malignant primary tumor of the central nervous system and is characterized by an extremely low overall survival. Recent breakthroughs in cancer therapy using immune checkpoint blockade have attracted significant attention. However, despite representing the most promising (immunotherapy) treatment for cancer, the clinical application of immune checkpoint blockade in glioma patients

    更新日期:2020-11-27
  • An Omalizumab Biobetter Antibody With Improved Stability and Efficacy for the Treatment of Allergic Diseases
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-29
    Peipei Liu; Zhongzong Pan; Chunyin Gu; Xiaodan Cao; Xiaowu Liu; Jianjian Zhang; Zheng Xiao; Xueping Wang; Haibing Guo; Dianwen Ju; Su-Jun Deng

    The critical role of IgE in allergic diseases is well-documented and clinically proven. Omalizumab, a humanized anti-IgE antibody, was the first approved antibody for the treatment of allergic diseases. Nevertheless, omalizumab still has some limitations, such as product instability and dosage restriction in clinical application. In this study, we attempted to develop an omalizumab biobetter antibody

    更新日期:2020-11-27
  • IL-7 During Antigenic Stimulation Using Allogeneic Dendritic Cells Promotes Expansion of CD45RA-CD62L+CD4+ Invariant NKT Cells With Th-2 Biased Cytokine Production Profile
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-29
    Abel Trujillo-Ocampo; Hyun-Woo Cho; Michael Clowers; Sumedha Pareek; Wilfredo Ruiz-Vazquez; Sung-Eun Lee; Jin S. Im

    Invariant natural killer T (iNKT) cells are innate-like T lymphocytes cells that recognize glycolipid antigens associated with CD1d, non-classical antigen presenting proteins. They can drive either pro-inflammatory (Th-1) or anti-inflammatory (Th-2) immune microenvironment through the production of both Th-1 and Th-2 type cytokines upon activation, thus play a vital role in cancer, infection, and autoimmune

    更新日期:2020-11-27
  • The Adipocyte and Adaptive Immunity
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-27
    Jianfeng Song; Tuo Deng

    Not only do Adipocytes have energy storage and endocrine functions, but they also play an immunological role. Adipocytes are involved in adaptive immunity to mediate the pathological processes of a variety of chronic inflammatory diseases and autoimmune syndromes. The adaptive immune response consists of T cell-mediated cellular immunity and B cell-mediated humoral immunity. Obese adipocytes overexpress

    更新日期:2020-11-27
  • Machine Learning to Quantify In Situ Humoral Selection in Human Lupus Tubulointerstitial Inflammation
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-27
    Andrew J. Kinloch; Yuta Asano; Azam Mohsin; Carole Henry; Rebecca Abraham; Anthony Chang; Christine Labno; Patrick C. Wilson; Marcus R. Clark

    In human lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ expansion of B cells expressing anti-vimentin antibodies (AVAs). The mechanism by which AVAs are selected is unclear. Herein, we demonstrate that AVA somatic hypermutation (SHM) and selection increase affinity for vimentin. Indeed, germline reversion of several antibodies demonstrated that higher affinity AVAs

    更新日期:2020-11-27
  • Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-27
    Chiara Niespolo; Jessica M. Johnston; Sumeet R. Deshmukh; Swapna Satam; Ziyanda Shologu; Oscar Villacanas; Ian M. Sudbery; Heather L. Wilson; Endre Kiss-Toth

    The pseudokinase TRIB1 controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation via the COP1 ubiquitin ligase. TRIB1 regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, TRIB1 has also been implicated in the pathogenesis of

    更新日期:2020-11-27
  • Phase I Trial of Fourth-Generation Anti-CD19 Chimeric Antigen Receptor T Cells Against Relapsed or Refractory B Cell Non-Hodgkin Lymphomas
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-26
    Xuan Zhou; Sanfang Tu; Chunsheng Wang; Rui Huang; Lan Deng; Chaoyang Song; Chunyan Yue; Yanjie He; Jilong Yang; Zhao Liang; Anqin Wu; Meifang Li; Weijun Zhou; Jingwen Du; Zhenling Guo; Yongqian Li; Cheng Jiao; Yuchen Liu; Lung-Ji Chang; Yuhua Li

    Background The administration of second- or third-generation anti-CD19 chimeric antigen receptor (CAR) T cells has remarkably improved the survival of patients with relapsed or refractory B cell malignancies. However, there are limited clinical results from fourth-generation CAR-T cell therapy, and the factors affecting response rate and survival have not been fully determined. Methods Lymphoma patients

    更新日期:2020-11-27
  • Basophils and Eosinophils in Nematode Infections
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-23
    Kazushige Obata-Ninomiya; Phillip P. Domeier; Steven F. Ziegler

    Helminths remain one of the most prolific pathogens in the world. Following infection helminths interact with various epithelial cell surfaces, including skin, lung, and gut. Recent works have shown that epithelial cells produce a series of cytokines such as TSLP, IL-33, and IL-25 that lead to the induction of innate and acquired type 2 immune responses, which we named Type 2 epithelial cytokines.

    更新日期:2020-11-27
  • Lipopolysaccharide Recognition in the Crossroads of TLR4 and Caspase-4/11 Mediated Inflammatory Pathways
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-23
    Alla Zamyatina; Holger Heine

    The innate immune response to lipopolysaccharide is essential for host defense against Gram-negative bacteria. In response to bacterial infection, the TLR4/MD-2 complex that is expressed on the surface of macrophages, monocytes, dendritic, and epithelial cells senses picomolar concentrations of endotoxic LPS and triggers the production of various pro-inflammatory mediators. In addition, LPS from extracellular

    更新日期:2020-11-27
  • Maturation of Monocyte-Derived DCs Leads to Increased Cellular Stiffness, Higher Membrane Fluidity, and Changed Lipid Composition
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-15
    Jennifer J. Lühr; Nils Alex; Lukas Amon; Martin Kräter; Markéta Kubánková; Erdinc Sezgin; Christian H. K. Lehmann; Lukas Heger; Gordon F. Heidkamp; Ana-Sunčana Smith; Vasily Zaburdaev; Rainer A. Böckmann; Ilya Levental; Michael L. Dustin; Christian Eggeling; Jochen Guck; Diana Dudziak

    Dendritic cells (DCs) are professional antigen-presenting cells of the immune system. Upon sensing pathogenic material in their environment, DCs start to mature, which includes cellular processes, such as antigen uptake, processing and presentation, as well as upregulation of costimulatory molecules and cytokine secretion. During maturation, DCs detach from peripheral tissues, migrate to the nearest

    更新日期:2020-11-27
  • Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-03
    Juan Francisco Gutiérrez-Bautista; Antonio Rodriguez-Nicolas; Antonio Rosales-Castillo; Pilar Jiménez; Federico Garrido; Per Anderson; Francisco Ruiz-Cabello; Miguel Ángel López-Ruz

    The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8

    更新日期:2020-11-27
  • Emerging Neuroblastoma 3D In Vitro Models for Pre-Clinical Assessments
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Diana Corallo; Stella Frabetti; Olivia Candini; Elisa Gregianin; Massimo Dominici; Horst Fischer; Sanja Aveic

    The potential of tumor three-dimensional (3D) in vitro models for the validation of existing or novel anti-cancer therapies has been largely recognized. During the last decade, diverse in vitro 3D cell systems have been proposed as a bridging link between two-dimensional (2D) cell cultures and in vivo animal models, both considered gold standards in pre-clinical settings. The latest awareness about

    更新日期:2020-11-27
  • Accurate and Efficient KIR Gene and Haplotype Inference From Genome Sequencing Reads With Novel K-mer Signatures
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    David Roe; Rui Kuang

    The killer-cell immunoglobulin-like receptor (KIR) proteins evolve to fight viruses and mediate the body’s reaction to pregnancy. These roles provide selection pressure for variation at both the structural/haplotype and base/allele levels. At the same time, the genes have evolved relatively recently by tandem duplication and therefore exhibit very high sequence similarity over thousands of bases. These

    更新日期:2020-11-27
  • Emerging Roles of Exosomes in T1DM
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Haipeng Pang; Shuoming Luo; Yang Xiao; Ying Xia; Xia Li; Gan Huang; Zhiguo Xie; Zhiguang Zhou

    Type 1 diabetes mellitus (T1DM) is a complex autoimmune disorder that mainly affects children and adolescents. The elevated blood glucose level of patients with T1DM results from absolute insulin deficiency and leads to hyperglycemia and the development of life-threatening diabetic complications. Although great efforts have been made to elucidate the pathogenesis of this disease, the precise underlying

    更新日期:2020-11-27
  • Specific Targeting of Lymphoma Cells Using Semisynthetic Anti-Idiotype Shark Antibodies
    Front. Immunol. (IF 5.085) Pub Date : 2020-11-02
    Arturo Macarrón Palacios; Julius Grzeschik; Lukas Deweid; Simon Krah; Stefan Zielonka; Thies Rösner; Matthias Peipp; Thomas Valerius; Harald Kolmar

    The B-cell receptor (BCR) is a key player of the adaptive immune system. It is a unique part of immunoglobulin (Ig) molecules expressed on the surface of B cells. In case of many B-cell lymphomas, the tumor cells express a tumor-specific and functionally active BCR, also known as idiotype. Utilizing the idiotype as target for lymphoma therapy has emerged to be demanding since the idiotype differs from

    更新日期:2020-11-27
  • Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-30
    Paal F. Brunsvig; Tormod Kyrre Guren; Marta Nyakas; Claudius H. Steinfeldt-Reisse; Wenche Rasch; Jon Amund Kyte; Hedvig Vidarsdotter Juul; Steinar Aamdal; Gustav Gaudernack; Else Marit Inderberg

    Human telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple epitopes identified by epitope spreading data from long-term survivors from previous hTERT vaccination

    更新日期:2020-11-27
  • GSK3β Plays a Negative Role During White Spot Syndrome Virus (WSSV) Infection by Regulating NF-κB Activity in Shrimp Litopenaeus vannamei
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-30
    Shuang Zhang; Lulu Zhu; Cuihong Hou; Hang Yuan; Sheng Yang; Mustafa Abdo Saif Dehwah; Lili Shi

    Glycogen synthase kinase-3 (GSK3), a cytoplasmic serine/threonine-protein kinase involved in a large number of key cellular processes, is a little-known signaling molecule in virus study. In this study, a GSK3 protein which was highly similar to GSK3β homologs from other species in Litopenaeus vannamei (designated as LvGSK3β) was obtained. LvGSK3β was expressed constitutively in the healthy L. vannamei

    更新日期:2020-11-27
  • Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-29
    Mahinbanu Mammadli; Weishan Huang; Rebecca Harris; Aisha Sultana; Ying Cheng; Wei Tong; Jeffery Pu; Teresa Gentile; Shanti Dsouza; Qi Yang; Alaji Bah; Avery August; Mobin Karimi

    Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Novel treatment strategies are needed which allow preservation of GVL effects without

    更新日期:2020-11-27
  • Gut–Liver Immune Response and Gut Microbiota Profiling Reveal the Pathogenic Mechanisms of Vibrio harveyi in Pearl Gentian Grouper (Epinephelus lanceolatus♂ × E. fuscoguttatus♀)
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-29
    Yiqin Deng; Yaqiu Zhang; Haoxiang Chen; Liwen Xu; Qian Wang; Juan Feng

    Vibrio harveyi causes vibriosis in nearly 70% of grouper (Epinephelus sp.), seriously limiting grouper culture. As well as directly inhibiting pathogens, the gut microbiota plays critical roles in immune homeostasis and provides essential health benefits to its host. However, there is still little information about the variations in the immune response to V. harveyi infection and the gut microbiota

    更新日期:2020-11-27
  • Hematopoietic Stem Cell Niches and Signals Controlling Immune Cell Development and Maintenance of Immunological Memory
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-29
    Runfeng Miao; Vivian Y. Lim; Neeharika Kothapalli; Yifan Ma; Julia Fossati; Sandra Zehentmeier; Ruifeng Sun; João P. Pereira

    Studies over the last couple of decades have shown that hematopoietic stem cells (HSCs) are critically dependent on cytokines such as Stem Cell Factor and other signals provided by bone marrow niches comprising of mesenchymal stem and progenitor cells (MSPCs) and endothelial cells (ECs). Because of their critical roles in HSC maintenance the niches formed by MSPCs and ECs are commonly referred to as

    更新日期:2020-11-27
  • Th17-Immune Response in Patients With Membranous Nephropathy Is Associated With Thrombosis and Relapses
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-28
    Marion Cremoni; Vesna Brglez; Sandra Perez; Fabrice Decoupigny; Kévin Zorzi; Marine Andreani; Alexandre Gérard; Sonia Boyer-Suavet; Caroline Ruetsch; Sylvia Benzaken; Vincent Esnault; Barbara Seitz-Polski

    Membranous nephropathy (MN) is a rare autoimmune kidney disease. Most autoimmune diseases are associated with a pro-inflammatory Th17-immune response, but little is known about immune dysregulation in MN. In China, MN was associated with exposure to fine air particulate matter (PM2.5) that could act as a danger signal and redirect immune response toward the Th2 or Th17 pathway. We aimed to analyze

    更新日期:2020-11-27
  • Interleukin-33 Promotes Cell Survival via p38 MAPK-Mediated Interleukin-6 Gene Expression and Release in Pediatric AML
    Front. Immunol. (IF 5.085) Pub Date : 2020-10-28
    Yiqian Wang; Haibo Su; Muxia Yan; Li Zhang; Jiancheng Tang; Quanxin Li; Xiaoqiong Gu; Qing Gong

    Acute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of immature myeloid blasts in the bone marrow (BM). Cytokine provide signals for leukemia cells to improve their survival in the BM microenvironment. Previously, we identified interleukin-33 (IL-33) as a promoter of cell survival in a human AML cell line and primary mouse leukemia cells. In this study, we report that

    更新日期:2020-11-27