Th17 is a newly identified T cell lineage that secretes the proinflamatory cytokine IL-17. Th17 cells have been shown to play a crucial role in mediating autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), arthritis, and colitis. However, recent study showed that donor Th17 cell ameliorated acute graft-versus-host disease (GVHD) due to the downregulation of Th1 differentiation in a murine BMT model. The role of IL-17 on developing chronic GVHD, which is pathologically similar to autoimmue diseases, remains unanswered. To this end, we compared the development of chronic GVHD between the lethally irradiated mice (Balb/c, H-2d) given IL-17 knockout(IL- 17KO, C57BL/6 background, H-2b) bone marrow (BM) cells and wild type BM cells with low dose WT splenocytes to induce sublethal acute GVHD and chronic GVHD subsequently. Up to day 60 after BMT no significant differences in clinical symptoms of GVHD including body weight changes were observed between the mice co-injected with IL-17 KO BM cells plus WT splenocytes and WT BM cells plus WT splenocytes. After day 60 the mice receiving WT BM cells plus WT splenocytes experienced weight loss accompanied by skin inflammatory changes, while mice receiving IL-17KO BM plus WT splenocytes showed minimal signs of GVHD as well as mice receiving IL-17 KO BM or WT BM alone. Recovery of body weight on day 160 after BMT was statistically different between two groups (p=0.035). Taken together, IL-17 was exacerbation factor of chronic GVHD, but not acute GVHD. Next we further evaluated the percentage of Th17 cells derived from BM cells (not from infused splenocytes) in the spleen on day 160 after BMT. Percentages of IL-17 expressing cells in the mice receiving WT BM plus WT splenocytes in spleen were significantly higher than those of WT BM alone receiving mice in CD4 (p=0.03) subpopulations. In conclusion, Th17 cells critically involved in the pathogenesis of chronic GVHD. Neutralizing IL-17 would be potent strategy for preventing chronic GVHD.

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Topics:
bone marrow, bone marrow transplantation, donors, experimental autoimmune encephalomyelitis, graft-versus-host disease, chronic, interleukin-17, mice, symptom aggravating factors, body weight changes, weight reduction

Disclosures: No relevant conflicts of interest to declare.

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2008, The American Society of Hematology
2008
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