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

被引:660
作者
Murai, Masako [1 ]
Turovskaya, Olga [1 ]
Kim, Gisen [1 ]
Madan, Rajat [2 ,3 ]
Karp, Christopher L. [2 ,3 ]
Cheroutre, Hilde [1 ]
Kronenberg, Mitchell [1 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Dev Immunol, La Jolla, CA USA
[2] Univ Cincinnati, Coll Med, Cincinnati, OH USA
[3] Cincinnati Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH USA
基金
美国国家卫生研究院;
关键词
IMMUNE-RESPONSES; CUTTING EDGE; TOLERANCE; INDUCE; INFLAMMATION; GENERATION; LINEAGE; IL-10; CURE;
D O I
10.1038/ni.1791
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Regulatory T cells (T-reg cells) that express the transcription factor Foxp3 suppress the activity of other cells. Here we show that interleukin 10 (IL-10) produced by CD11b(+) myeloid cells in recombination-activating gene 1-deficient (Rag1(-/-)) recipient mice was needed to prevent the colitis induced by transferred CD4(+)CD45RB(hi) T cells. In Il10(-/-)Rag1(-/-) mice, T-reg cells failed to maintain Foxp3 expression and regulatory activity. The loss of Foxp3 expression occurred only in recipients with colitis, which indicates that the requirement for IL-10 is manifested in the presence of inflammation. IL-10 receptor-deficient (Il10rb(-/-)) T-reg cells also failed to maintain Foxp3 expression, which suggested that host IL-10 acted directly on the T-reg cells. Our data indicate that IL-10 released from myeloid cells acts in a paracrine manner on T-reg cells to maintain Foxp3 expression.
引用
收藏
页码:1178 / U61
页数:8
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