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      IL17-Producing γδ T Cells May Enhance Humoral Immunity during Pulmonary Pseudomonas aeruginosa Infection in Mice

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          Abstract

          The host acquired immune response, especially the humoral immunity, plays key roles in preventing bacterial pneumonia in the lung. Our previous research demonstrated that interleukin 17-producing γδ T cells (IL17-γδ T cells) have a protective effect on the early innate immune response during acute pulmonary Pseudomonas aeruginosa infection. However, whether IL17-γδ T cells also play a role in humoral immunity is unknown. In this study, an acute pulmonary P. aeruginosa infection model was established in wild-type and γδ TCR −/− C57BL/6 mice. The expression of IL-17 on γδ T cells isolated from infected lung tissues increased rapidly and peaked at day 7 after acute infection with P. aeruginosa. Compared with wild-type infected mice, the levels of total immunoglobulins including IgA, IgG, and IgM in the serum and BALF were significantly decreased in γδ TCR −/− mice, with the exception of IgM in the BALF. Moreover, CD69 expression in B cells from the lungs and spleen and the level of BAFF in the plasma were also decreased in γδ TCR −/− mice. IL17-γδ T cell transfusion significantly improved the production of immunoglobulins, B cell activation and BAFF levels in γδ TCR −/− mice compared with γδ TCR −/− mice without transfusion; this effect was blocked when cells were pretreated with an IL-17 antibody. Together, these data demonstrate that IL17-γδ T cells are involved in CD19 + B cell activation and the production of immunoglobulins during acute pulmonary P. aeruginosa infection. Thus, we conclude that IL17-γδ T cells may facilitate the elimination of bacteria and improve survival through not only innate immunity but also humoral immunity.

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          Most cited references27

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          Mediators of Inflammation in Acute Kidney Injury

          Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is now believed to play a major role in the pathopathophysiology of AKI. It is hypothesized that in ischemia, sepsis and nephrotoxic models that the initial insult results in morphological and/or functional changes in vascular endothelial cells and/or in tubular epithelium. Then, leukocytes including neutrophils, macrophages, natural killer cells, and lymphocytes infiltrate into the injured kidneys. The injury induces the generation of inflammatory mediators like cytokines and chemokines by tubular and endothelial cells which contribute to the recruiting of leukocytes into the kidneys. Thus, inflammation has an important role in the initiation and extension phases of AKI. This review will focus on the mediators of inflammation contributing to the pathogenesis of AKI.
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            IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection.

            IL-17 is a cytokine produced by T cells in response to IL-23. Recent data support a new subset of CD4 Th cells distinct from Th1 or Th2 cells that produce IL-17 and may contribute to inflammation. In this study, we demonstrate that, in naive mice, as well as during Mycobacterium tuberculosis infection, IL-17 production is primarily from gammadelta T cells and other non-CD4(+)CD8(+) cells, rather than CD4 T cells. The production of IL-17 by these cells is stimulated by IL-23 alone, and strongly induced by the cytokines, including IL-23, produced by M. tuberculosis-infected dendritic cells. IL-23 is present in the lungs early in infection and the IL-17-producing cells, such as gammadelta T cells, may represent a central innate protective response to pulmonary infection.
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              B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells.

              BAFF (B cell-activating factor belonging to the TNF family) is a cell survival and maturation factor for B cells, and overproduction of BAFF is associated with systemic autoimmune disease. BAFF binds to three receptors, BAFF-R, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation Ag (BCMA). Using specific mAbs, BAFF-R was found to be the predominant BAFF receptor expressed on peripheral B cells, in both humans and mice, and antagonist mAbs to BAFF-R blocked BAFF-mediated costimulation of anti- micro responses. The other BAFF receptors showed a much more restricted expression pattern, suggestive of specialized roles. BCMA was expressed by germinal center B cells, while TACI was expressed predominantly by splenic transitional type 2 and marginal zone B cells, as well as activated B cells, but was notably absent from germinal center B cells. BAFF was also an effective costimulator for T cells, and this costimulation occurs entirely through BAFF-R. BAFF-R, but not TACI or BCMA, was expressed on activated/memory subsets of T cells, and T cells from BAFF-R mutant A/WySnJ mice failed to respond to BAFF costimulation. Thus, BAFF-R is important not only for splenic B cell maturation, but is the major mediator of BAFF-dependent costimulatory responses in peripheral B and T cells.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                06 December 2016
                2016
                : 6
                : 170
                Affiliations
                Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine Shanghai, China
                Author notes

                Edited by: Thomas A. Ficht, Texas A&M University, USA

                Reviewed by: Ashu Sharma, University at Buffalo, USA; Elizabeth B. Norton, Tulane University, USA

                *Correspondence: Jialin Liu fillelibra@ 123456hotmail.com

                †These authors have contributed equally to this work.

                Article
                10.3389/fcimb.2016.00170
                5138229
                27999768
                3fffbf1d-8e59-48a9-bf35-97188f4e85b1
                Copyright © 2016 Pan, Tan, Li, Liu, Wang, Tian, Liu and Qu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 July 2016
                : 15 November 2016
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 34, Pages: 8, Words: 5644
                Funding
                Funded by: Natural Science Foundation of Shanghai 10.13039/100007219
                Award ID: 16ZR1420900
                Categories
                Microbiology
                Original Research

                Infectious disease & Microbiology
                il17-γδ t cells,b cells,b cell activating factor,immunoglobulin(s)

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