| First Author | Kayama H | Year | 2019 |
| Journal | Int Immunol | Volume | 31 |
| Issue | 6 | Pages | 371-383 |
| PubMed ID | 30753547 | Mgi Jnum | J:276847 |
| Mgi Id | MGI:6306591 | Doi | 10.1093/intimm/dxz014 |
| Citation | Kayama H, et al. (2019) BATF2 prevents T-cell-mediated intestinal inflammation through regulation of the IL-23/IL-17 pathway. Int Immunol 31(6):371-383 |
| abstractText | Inappropriate activation of the IL-23 signaling pathway causes chronic inflammation through the induction of immunopathological Th17 cells in several tissues including the intestine, whereas adequate Th17 responses are essential for host defense against harmful organisms. In the intestinal lamina propria, IL-23 is primarily produced by innate myeloid cells including dendritic cells (DCs) and macrophages (Mvarphis). However, the molecular mechanisms underlying the regulation of IL-23 production by these cells remains poorly understood. In this study, we demonstrated that BATF2 regulates intestinal homeostasis by inhibiting IL-23-driven T-cell responses. Batf2 was highly expressed in intestinal innate myeloid subsets, such as monocytes, CD11b+ CD64+ Mvarphis and CD103+ DCs. Batf2-/- mice spontaneously developed colitis and ileitis with altered microbiota composition. In this context, IL-23, but not TNF-alpha and IL-10, was produced in high quantities by intestinal CD11b+ CD64+ Mvarphis from Batf2-/- mice compared with wild-type mice. Moreover, increased numbers of IFN-gamma+, IL-17+ and IFN-gamma+ IL-17+ CD4+ T cells, but not IL-10+ CD4+ T cells, accumulated in the colons and small intestines of Batf2-/- mice. In addition, RORgammat-expressing innate lymphoid cells were increased in Batf2-/- mice. Batf2-/-Rag2-/- mice showed a reduction in intestinal inflammation present in Batf2-/- mice. Furthermore, the high numbers of intestinal IL-17+ and IFN-gamma+ IL-17+ CD4+ T cells were markedly reduced in Batf2-/- mice when introducing Il23a deficiency, which was associated with the abrogation of intestinal inflammation. These results indicated that BATF2 in innate myeloid cells is a key molecule for the suppression of IL-23/IL-17 pathway-mediated adaptive intestinal pathology. |
