Control of T_H17 cells occurs in the small intestine

Esplugues E et al., Nature 475:514-518, 2011

Speaker: Yung-Tsai Liou (劉勇材)                                        Time: 14:00-15:00, Oct. 26, 2011

Commentator: Dr. Bei-Chang Yang (楊倍昌 老師)            Place: Room 601

Abstract

T_H17 cells, named by their secretion of IL-17, protect the host from pathogen invasion.  However, they may cause tissue damages in some autoimmune diseases such as multiple sclerosis and rheumatoid arthritis¹.  TGF-b, IL-6 and IL-23 are key initiation cytokines for T_H17 cell differentiation.  In a CD3-specfic antibody-treated mouse model, high levels of TGF-b, IL-6 and IL-17 caused intestine inflammation.  Interestingly, the numbers of T lymphocytes were decreased in peripheral blood but increased in the intestine after anti-CD3 injection.  The authors found that a large number of T_H17 cells migrated to the small intestine of IL-17A–eGFP knock-in mice after anti-CD3 injection.  The CCR6/CCL20 axis has been shown to mediate immune cell migration to the small intestine².  Indeed, IL-17 induced high expression levels of CCL20 in intestine, and T_H17 cell migration to the intestine was significantly reduced in anti-CD3 treated Ccr6^-/- mice.  Importantly, acute intestine inflammation induced by anti-CD3 was transient and all mice fully recovered.  Thus, these results implied that there might be a negative regulatory mechanism in the intestine. Anti-CD3 treatment did not trigger T_H17 cell apoptosis at late stage.   Using microarray analysis, the authors found that anti-CD3-stimulated T_H17 cells expressed higher level of IL-10 than the pathogenic T_H17 cells from experimental autoimmune encephalomyelitis, a mouse model of human multiple sclerosis.  In both in vitro suppression assay and in vivo adoptive transfer assay, the anti-CD3-induced T_H17 cells displayed a strong suppressive capacity via their secretion of anti-inflammatory cytokine IL-10.  The regulatory T_H17 (rT_H17) cells could also be observed in the small intestine during sepsis and H1N1 infection.  In conclusion, the authors have identified rT_H17 cells that may suppress the immunopathogenic inflammation in small intestine after clearance of infectious agents.

References

1.      Tesmer LA et al., T_H17 cells in human disease. Immunol. Rev. 223:87-113, 2008

2.      Williams IR et al., CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis. Ann. N. Y. Acad. Sci. 1072:52-61, 2006