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Frontiers in Immunology

Caiyan Zhang, Jinrong Fu, Yufeng Zhou
Over 100 types of cellular RNA modifications have been identified in both coding and a variety of non-coding RNAs. N6-methyladenosine (m6A) is the most prevalent and abundant post-transcriptional RNA modification on eukaryote mRNA, and its biological functions are mediated by special binding proteins (i.e., methyltransferases, demethylases, and effectors) that recognize this modification. The presence of m6A on transcripts contributes to diverse fundamental cellular functions, such as pre-mRNA splicing, nuclear transport, stability, translation, and microRNA biogenesis, implying an association with numerous human diseases...
2019: Frontiers in Immunology
Rui Yang, Lan Yao, Ling Shen, Wei Sha, Robert L Modlin, Hongbo Shen, Zheng W Chen
While IL-12 plays a key role in differentiation of protective CD4+ Th1 response, little is known about mechanisms whereby IL-12 differentiates other T-cell populations. Published studies suggest that predominant Vγ2Vδ2 T cells in humans/nonhuman primates (NHP) are a fast-acting T-cell subset, with capacities to rapidly expand and produce Th1 and cytotoxic cytokines in response to phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by Mycobacterium tuberculosis (Mtb) or others. However, whether IL-12 signaling pathway mediates fast-acting and Th1 or anti-microbial features of Vγ2Vδ2 T cells remains poorly defined...
2019: Frontiers in Immunology
Jassy Mary S Lazarte, Kim D Thompson, Tae Sung Jung
Teleost fish, as with other vertebrates, rely on their innate immune system as a first line of defense against invading pathogens. A very important characteristic of the innate immune response is its ability to recognize conserved molecular structures, such as viral dsRNA and ssRNA. Mda5 is one of the three pattern recognition receptors (PRRs) that recognize cytoplasmic viral ligands. Teleost Mda5 is widely conserved among several fish species and possesses the same structural domains as those seen in their mammalian counterparts...
2019: Frontiers in Immunology
Tobias Heigl, Anurag Singh, Berta Saez-Gimenez, Janne Kaes, Anke Van Herck, Annelore Sacreas, Hanne Beeckmans, Arno Vanstapel, Stijn E Verleden, Dirk E Van Raemdonck, Geert Verleden, Bart M Vanaudenaerde, Dominik Hartl, Robin Vos
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage. MDSCs expand in pathological situations, such as chronic infection, cancer, autoimmunity, and allograft rejection. As chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation (LTx), MDSCs may play a role in its pathophysiology. We assessed phenotype and frequency of MDSCs in peripheral blood from lung transplant recipients and its relationship to post-transplant complications and immunosuppression...
2019: Frontiers in Immunology
Kuldeep Kumawat, Ruben J Geerdink, Marije P Hennus, Mojtaba Abdul Roda, Ingrid van Ark, Thea Leusink-Muis, Gert Folkerts, Anita van Oort-Jansen, Alexandra Mazharian, Steve P Watson, Frank E Coenjaerts, Louis Bont, Linde Meyaard
Neutrophils are crucial to antimicrobial defense, but excessive neutrophilic inflammation induces immune pathology. The mechanisms by which neutrophils are regulated to prevent injury and preserve tissue homeostasis are not completely understood. We recently identified the collagen receptor leukocyte-associated immunoglobulin-like receptor (LAIR)-1 as a functional inhibitory receptor on airway-infiltrated neutrophils in viral bronchiolitis patients. In the current study, we sought to examine the role of LAIR-1 in regulating airway neutrophil responses in vivo ...
2019: Frontiers in Immunology
Nyambayar Dashtsoodol, Sabrina Bortoluzzi, Marc Schmidt-Supprian
The CD1d-restricted Vα14 invariant NKT (iNKT) cell lineage in mice (Vα24 in humans) represents an evolutionary conserved innate-like immune cell type that recognizes glycolipid antigens. Because of their unique ability to promptly secrete copious amounts of both pro-inflammatory and anti-inflammatory cytokines, typically produced by different T helper cell types, iNKT cells are implicated in the regulation of various pathologic conditions such as infection, allergy, autoimmune disease, maintenance of transplantation tolerance, and cancer...
2019: Frontiers in Immunology
Talita Duarte Pagani, Ana Carolina R Guimarães, Mariana C Waghabi, Paloma Rezende Corrêa, Dário Eluan Kalume, Marcia Berrêdo-Pinho, Wim Maurits Degrave, Leila Mendonça-Lima
Surface-associated proteins from Mycobacterium bovis BCG Moreau RDJ are important components of the live Brazilian vaccine against tuberculosis. They are important targets during initial BCG vaccine stimulation and modulation of the host's immune response, especially in the bacterial-host interaction. These proteins might also be involved in cellular communication, chemical response to the environment, pathogenesis processes through mobility, colonization, and adherence to the host cell, therefore performing multiple functions...
2019: Frontiers in Immunology
Caterina Curato, Biana Bernshtein, Eva Zupancič, Almut Dufner, Diego Jaitin, Amir Giladi, Eyal David, Louise Chappell-Maor, Dena Leshkowitz, Klaus-Peter Knobeloch, Ido Amit, Helena F Florindo, Steffen Jung
Dendritic cells (DC) are unrivaled in their potential to prime naive T cells by presenting antigen and providing costimulation. DC are furthermore believed to decode antigen context by virtue of pattern recognition receptors and to polarize T cells through cytokine secretion toward distinct effector functions. Diverse polarized T helper (TH ) cells have been explored in great detail. In contrast, studies of instructing DC have to date largely been restricted to in vitro settings or adoptively transferred DC...
2019: Frontiers in Immunology
Stefanie K Wculek, Sofía C Khouili, Elena Priego, Ignacio Heras-Murillo, David Sancho
Dendritic cells (DCs) control innate and adaptive immunity by patrolling tissues to gather antigens and danger signals derived from microbes and tissue. Subsequently, DCs integrate those environmental cues, orchestrate immunity or tolerance, and regulate tissue homeostasis. Recent advances in the field of immunometabolism highlight the notion that immune cells markedly alter cellular metabolic pathways during differentiation or upon activation, which has important implications on their functionality. Previous studies showed that active oxidative phosphorylation in mitochondria is associated with immature or tolerogenic DCs, while increased glycolysis upon pathogen sensing can promote immunogenic DC functions...
2019: Frontiers in Immunology
Amanda Cabral, Darlan da Silva Cândido, Sandra Maria Monteiro, Francine Lemos, David Saitovitch, Irene L Noronha, Letícia Ferreira Alves, Murilo Vieira Geraldo, Jorge Kalil, Edecio Cunha-Neto, Ludmila Rodrigues Pinto Ferreira, Verônica Coelho
Background: Operational tolerance (OT) is a state of graft functional stability that occurs after at least 1 year of immunosuppressant withdrawal. MicroRNAs ( microRNA ) are small non-coding RNAs that downregulate messenger RNA/protein expression of innumerous molecules and are critical for homeostasis. We investigated whether OT in kidney transplantation displays a differential microRNA profile, which would suggest that microRNAs participate in Operational Tolerance mechanisms, and may reveal potential molecular pathways...
2019: Frontiers in Immunology
Tamarah D de Jong, Tanja Snoek, Elise Mantel, Conny J van der Laken, Ronald F van Vollenhoven, Willem F Lems
Objective: The type I interferon (IFN) response in rheumatoid arthritis (RA) has been extensively studied in relation to therapy with biological DMARDs (bDMARDs). However, the effect of conventional synthetic (cs)DMARDs and glucocorticoids (GCs) on IFN response gene (IRG) expression remains largely unknown, even though csDMARDS are used throughout all disease phases, including simultaneously with biologic therapy. This study was aimed to determine the dynamics of IFN response upon immunosuppressive treatment...
2019: Frontiers in Immunology
Jinchao Jia, Hui Shi, Mengguo Liu, Tingting Liu, Jieyu Gu, Liyan Wan, Jialin Teng, Honglei Liu, Xiaobing Cheng, Junna Ye, Yutong Su, Yue Sun, Wen Gong, Chengde Yang, Qiongyi Hu
Previous studies have revealed that several micro-organisms, especially DNA viruses, have been associated with adult-onset Still's disease (AOSD). However, there are no studies on the relationship between the presence of viral infections in AOSD patients with disease occurrence and reactivation. In the present study, we aimed to investigate the presence of antibodies against virus, virus DNA load and nucleic acid sensors in AOSD patients. Anti-viral antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples from 100 AOSD patients and 70 healthy controls (HCs)...
2019: Frontiers in Immunology
Chris John Weston, Henning Wolfgang Zimmermann, David H Adams
Control of homeostasis and rapid response to tissue damage in the liver is orchestrated by crosstalk between resident and infiltrating inflammatory cells. A crucial role for myeloid cells during hepatic injury and repair has emerged where resident Kupffer cells, circulating monocytes, macrophages, dendritic cells and neutrophils control local tissue inflammation and regenerative function to maintain tissue architecture. Studies in humans and rodents have revealed a heterogeneous population of myeloid cells that respond to the local environment by either promoting regeneration or driving the inflammatory processes that can lead to hepatitis, fibrogenesis, and the development of cirrhosis and malignancy...
2019: Frontiers in Immunology
Fadi Issa, Kate Milward, Ryoichi Goto, Gareth Betts, Kathryn J Wood, Joanna Hester
Regulatory T cells (Tregs) can control excessive or undesirable immune responses toward autoantigens, alloantigens, and pathogens. In transplantation, host immune responses against the allograft are suppressed through the use of immunosuppressive drugs, however this often results in life-threatening side effects including nephrotoxicity and an increased incidence of cancer and opportunistic infections. Tregs can control graft-vs.-host disease and transplant rejection in experimental models, providing impetus for the use of Tregs as a cellular therapy in clinical transplantation...
2019: Frontiers in Immunology
Fernando Corvillo, Marcin Okrój, Pilar Nozal, Marta Melgosa, Pilar Sánchez-Corral, Margarita López-Trascasa
Nephritic factors comprise a heterogeneous group of autoantibodies against neoepitopes generated in the C3 and C5 convertases of the complement system, causing its dysregulation. Classification of these autoantibodies can be clustered according to their stabilization of different convertases either from the classical or alternative pathway. The first nephritic factor described with the capacity to stabilize C3 convertase of the alternative pathway was C3 nephritic factor (C3NeF). Another nephritic factor has been characterized by the ability to stabilize C5 convertase of the alternative pathway (C5NeF)...
2019: Frontiers in Immunology
Fang Wang, Aishu Luo, Wenhua Xuan, Liang Qi, Qing Wu, Ke Gan, Qiande Zhang, Miaojia Zhang, Wenfeng Tan
Objectives: To determine the relationship between bone marrow edema (BME), synovitis, and bone erosion longitudinally using a collagen induced arthritis mice (CIA) model and to explore the potential pathogenic role of BME in bone erosion. Methods: CIA was induced in DBA/1J mice. BME and corresponding clinical symptoms of arthritis and synovitis during the different time points of CIA development were assayed by magnetic resonance imaging (MRI), arthritis sore, and histologic analyses. The expression of osteoclasts (OCs), OCs-related cytokines, and immune cells in bone marrow were determined by flow cytometry, immunohistochemistry, immunofluorescence staining, and real-time PCR...
2019: Frontiers in Immunology
Mauricio Campos-Mora, Pamina Contreras-Kallens, Felipe Gálvez-Jirón, Masyelly Rojas, Carolina Rojas, Aarón Refisch, Oscar Cerda, Karina Pino-Lagos
Several mechanisms of immune suppression have been attributed to Foxp3+ T regulatory cells (Treg) including modulation of target cells via inhibition of cell proliferation, alteration of cytokine secretion, and modification of cell phenotype, among others. Neuropilin-1 (Nrp1), a co-receptor protein highly expressed on Treg cells has been involved in tolerance-mediated responses, driving tumor growth and transplant acceptance. Here, we extend our previous findings showing that, despite expressing Foxp3, Nrp1KO Treg cells have deficient suppressive function in vitro in a contact-independent manner...
2019: Frontiers in Immunology
Osman K Yilmaz, Stefanie Haeberle, Meifeng Zhang, Marvin J Fritzler, Alexander H Enk, Eva N Hadaschik
Due to a missense mutation in the Foxp3 gene, scurfy mice are deficient in functional regulatory T cells (Treg). The consequent loss of peripheral tolerance manifests itself by fatal autoimmune mediated multi-organ disease. Previous studies have outlined the systemic inflammatory disease and demonstrated production of anti-nuclear antibodies (ANA) in scurfy mice. However, specific autoantibody targets remained to be defined. ANA are immunological markers for several connective tissue diseases (CTD) and target a large number of intracellular molecules...
2019: Frontiers in Immunology
Kirsten Geneugelijk, Kirsten A Thus, Hanneke W M van Deutekom, Jorg J A Calis, Eric Borst, Can Keşmir, Machteld Oudshoorn, Bronno van der Holt, Ellen Meijer, Sacha Zeerleder, Marco R de Groot, Peter A von dem Borne, Nicolaas Schaap, Jan Cornelissen, Jürgen Kuball, Eric Spierings
HLA-mismatches in hematopoietic stem-cell transplantation are associated with an impaired overall survival (OS). The aim of this study is to explore whether the Predicted Indirectly ReCognizable HLA-Epitopes (PIRCHE) algorithm can be used to identify HLA-mismatches that are related to an impaired transplant outcome. PIRCHE are computationally predicted peptides derived from the patient's mismatched-HLA molecules that can be presented by donor-patient shared HLA. We retrospectively scored PIRCHE numbers either presented on HLA class-I (PIRCHE-I) or class-II (PIRCHE-II) for a Dutch multicenter cohort of 103 patients who received a single HLA-mismatched (9/10) unrelated donor transplant in an early phase of their disease...
2019: Frontiers in Immunology
Hyungtaek Jeon, Jisu Lee, Suhyuk Lee, Su-Kyung Kang, Sang June Park, Seung-Min Yoo, Myung-Shin Lee
Kaposi's Sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma, which is the most common cancer in acquired immune deficiency syndrome patients. KSHV contains a variety of immunoregulatory proteins. There have been many studies on the modulation of antiviral response by these immunoregulatory proteins of KSHV. However, the antiviral effects of extracellular vesicles (EVs) during de novo KSHV infection have not been investigated to our best knowledge. In this study, we showed that KSHV-infected cells induce interferon-stimulated genes (ISGs) response but not type I interferon in uninfected bystander cells using EVs...
2019: Frontiers in Immunology
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