Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 15, Issue 3, Pages 233-245Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2016.37
Keywords
aGVHD; BMT; CD4(+) T cells; IL-17; Th17 cells
Categories
Funding
- National Natural Science Foundation of China [81273268, 81471586, 81273259, 81471589, 81500145]
- Natural Science Foundation of Jiangsu Province [BK20150352]
- Suzhou city [SWG0904]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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The role of IL-17 and IL-17-producing CD4(+) T cells in acute graft-versus-host disease ( GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4(+) T cells exacerbated acute GVHD compared with IL-17(-/-) CD4(+) T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4(+) T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs. Furthermore, IL-17 reduced the infiltration of macrophages into the GVHD tissues. In vitro study showed that IL-17 could downregulate Th1 responses, possibly through inhibiting IL-12 production by donor macrophages. Depletion of macrophages in vivo diminished the protective effect of IL-17. Our results demonstrated the differential roles of adoptively transferred donor IL-17-producing CD4(+) T cells and IL-17 in the same acute GVHD model.
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