Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis

NATURE IMMUNOLOGY. 2009 Nov;10(11):1141-3

Speaker: Wen-Ling Yeh (葉玟伶)                                    Time: 13:00~14:00 Apr.7, 2010

Commentator: Dr. Jiu-Yao Wang (王志堯 老師)       Place: Room 601

Abstract:

Regulatory T cells (Treg cells) are a subset of CD4⁺ T cells, which have suppression ability in T cell immune responses. Thus, many studies have attempted to prevent or rescue inflammatory autoimmune diseases such as multiple sclerosis and colitis by Treg cells transferation^[1]. Tregs cells express the transcription factor Foxp3, a major regulator of Treg cell development and function^[2]. The authors suggested that IL-10 is essential for Treg cells because mice deficient in either IL-10 or the IL-10 receptor β-chain develop spontaneous large intestine inflammation. To clarify whether IL-10 is required for suppression function of Treg cells and which cell type produce IL-10, the authors transfered CD4⁺CD45RB^hi T cells to Rag1^-/- mice, an animal model of colitis. They found that IL-10 derived from Treg cells was useless for the colitis prevention. In contrast, IL-10 produced from host was required for maintaining Foxp3 expression and colitis prevention. Further, they noted that Treg cells lost Foxp3 expression in inflammatory condition. Next, they identified which cell type producing IL-10 by transferring Terg cells and CD4⁺CD45RB^hi T cells into IL-10-producing nonlymphoid mice. Surprisingly, the cells expressing CD11b, CD11c and macrophage markers produced abundant IL-10 after transferring. Finally, they found that IL-10 produced by these CD11b⁺ cells played an essential role for Treg Foxp3 maintenance. In conclusion, host CD11b⁺CD11c⁺ myeloid cells are major producers of IL-10 to maintain Foxp3 expression in Treg cells to prevent inflammatory intestine disease.

References:

1.      Derya Unutmaz, et al.The gut feeling of Treg cells: IL-10 is the silver lining during colitis. Nat Immunol. 2009 Nov;10(11):1178-84.

2.      Sakaguchi, et al. Regulatory T Cells and Immune Tolerance. Cell. 2008 May 30;133(5):775-87.