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.

20 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Frontiers in Immunology 06/2014; 5:154. DOI:10.3389/fimmu.2014.00154
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Autoimmunity reviews 05/2014; 13(8). DOI:10.1016/j.autrev.2014.05.006 · 7.93 Impact Factor
  • Source
    • "T follicular helper (Tfh) cells are required both for affinity maturation and for the differentiation of germinal center B cells into plasma cells (Zotos et al., 2010). In the PP, a specific subset of Tfh cells has been shown to control the class switch of mucosal B cells to IgA-expressing plasmablasts (Hirota et al., 2013; Tsuji et al., 2009). The newly generated plasmablasts leave the PP and migrate through the blood circulation, and a fraction of them home to the LP. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although in normal lamina propria (LP) large numbers of eosinophils are present, little is known about their role in mucosal immunity at steady state. Here we show that eosinophils are needed to maintain immune homeostasis in gut-associated tissues. By using eosinophil-deficient ΔdblGATA-1 and PHIL mice or an eosinophil-specific depletion model, we found a reduction in immunoglobulin A(+) (IgA(+)) plasma cell numbers and in secreted IgA. Eosinophil-deficient mice also showed defects in the intestinal mucous shield and alterations in microbiota composition in the gut lumen. In addition, TGF-β-dependent events including class switching to IgA in Peyer's patches (PP), the formation of CD103(+) T cells including Foxp3(+) regulatory (Treg), and also CD103(+) dendritic cells were disturbed. In vitro cultures showed that eosinophils produce factors that promote T-independent IgA class switching. Our findings show that eosinophils are important players for immune homeostasis in gut-associated tissues and add to data suggesting that eosinophils can promote tissue integrity.
    Immunity 04/2014; 40(4):582-93. DOI:10.1016/j.immuni.2014.02.014 · 21.56 Impact Factor
Show more

Preview (2 Sources)

20 Reads
Available from