Hirota, K. et al. Plasticity of Th17 cells in Peyer’s patches is responsible for the induction of T cell-dependent IgA responses. Nat. Immunol. 14, 372-379

1] Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK. [2].
Nature Immunology (Impact Factor: 20). 03/2013; 14(4). DOI: 10.1038/ni.2552
Source: PubMed


Intestinal Peyer's patches are essential lymphoid organs for the generation of T cell-dependent immunoglobulin A (IgA) for gut homeostasis. Through the use of interleukin 17 (IL-17) fate-reporter mice, we found here that endogenous cells of the TH17 subset of helper T cells in lymphoid organs of naive mice 'preferentially' homed to the intestines and were maintained independently of IL-23. In Peyer's patches, such TH17 cells acquired a follicular helper T cell (TFH cell) phenotype and induced the development of IgA-producing germinal center B cells. Mice deficient in TH17 cells failed to generate antigen-specific IgA responses, which provides evidence that TH17 cells are the crucial subset required for the production of high-affinity T cell-dependent IgA.

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    • "Recent studies have highlighted novel roles for effector T cell subsets, such as Th17 and Tfh cells, in ectopic lymphoid neogenesis and the control of GC reactions (Lu et al., 2011; Peters et al., 2011; Rangel-Moreno et al., 2011; Hirota et al., 2013). Thus, cytokines linked with either T cell differentiation or plasticity of effector T cells into Tfh-like phenotypes may regulate ELS involvement in chronic disease (Lu et al., 2011; Peters et al., 2011; Hirota et al., 2013). As IL-27 inhibits effector Th17 responses, we considered the expression of Th17 and Tfh cell markers within the inflamed synovium. "
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    ABSTRACT: Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R-deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment.
    Full-text · Article · Sep 2015 · Journal of Experimental Medicine
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    • "This suggestion is somewhat controversial, as recent studies have implicated Th17 cells rather than Tregs in the induction of IgA in the gut (22, 23). Cao et al. implicated the mammalian specific cytokine IL17a in the production of IgA to flagellin. "
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    ABSTRACT: Although current thinking has focused on genetic variation between individuals and environmental influences as underpinning susceptibility to both autoimmunity and cancer, an alternative view is that human susceptibility to these diseases is a consequence of the way the immune system evolved. It is important to remember that the immunological genes that we inherit and the systems that they control were shaped by the drive for reproductive success rather than for individual survival. It is our view that human susceptibility to autoimmunity and cancer is the evolutionarily acceptable side effect of the immune adaptations that evolved in early placental mammals to accommodate a fundamental change in reproductive strategy. Studies of immune function in mammals show that high affinity antibodies and CD4 memory, along with its regulation, co-evolved with placentation. By dissection of the immunologically active genes and proteins that evolved to regulate this step change in the mammalian immune system, clues have emerged that may reveal ways of de-tuning both effector and regulatory arms of the immune system to abrogate autoimmune responses whilst preserving protection against infection. Paradoxically, it appears that such a detuned and deregulated immune system is much better equipped to mount anti-tumor immune responses against cancers.
    Full-text · Article · Jun 2014 · Frontiers in Immunology
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    • "Nossent, Australia). IL-17 is a known proinflammatory cytokine produced by T cells in order to recruit monocytes and neutrophils to the site of inflammation [28] [29] along with other Th17 cytokines [29] [30] [31] [32] [33] [34], and it is currently under investigation in several clinical studies as target of anti-inflammatory therapies for diseases such as psoriasis and multiple sclerosis [35]. Another cellular mechanism studied for its possible involvement in SLE is the identification of abnormalities of plasmacytoid dendritic cells that contribute to disease onset (V. "
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    ABSTRACT: Our understanding of the pathogenic mechanisms and possible treatments of autoimmune diseases has significantly increased over the past decade. Nonetheless, numerous major issues remain open and such issues span from epidemiology to clinimetrics, from the role of infectious agents to the search for accurate biomarkers in paradigmatic conditions such as systemic lupus erythematosus, rheumatoid arthritis, and spondiloarthropathies. In the case of cardiovascular comorbidities of autoimmune diseases or, more generally, the pathogenesis of atherosclerosis, fascinating evidence points to a central role of autoimmunity and metabolic dysfunctions and a possible role of therapies targeting inflammation to ameliorate both conditions. Basic science and translational medicine contribute to identify common mechanisms that underlie different autoimmune diseases, as in the case of tumor necrosis factor alpha, and more recently vitamin D, autoantibodies, T and B regulatory cells, and microRNA. Finally, new therapies are expected to significantly change our approach to autoimmune diseases, as represented by the recent FDA approval of the first oral Jak inhibitor. The present article moves from the major topics that were discussed at the 2013 Asian Congress of Autoimmunity in Hong Kong to illustrate the most recent data from leading journals in autoimmunity and immunology.
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