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

被引:668
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
相关论文
共 36 条
[1]   CD25+ CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10 [J].
Annacker, O ;
Pimenta-Araujo, R ;
Burlen-Defranoux, O ;
Barbosa, TC ;
Cumano, A ;
Bandeira, A .
JOURNAL OF IMMUNOLOGY, 2001, 166 (05) :3008-3018
[2]   An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation [J].
Asseman, C ;
Mauze, S ;
Leach, MW ;
Coffman, RL ;
Powrie, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (07) :995-1003
[3]   Colitogenic Th1 cells are present in the antigen-experienced T cell pool in normal mice:: Control by CD4+ regulatory T cells and IL-10 [J].
Asseman, C ;
Read, S ;
Powrie, F .
JOURNAL OF IMMUNOLOGY, 2003, 171 (02) :971-978
[4]   Interleukin-10 determines viral clearance or persistence in vivo [J].
Brooks, David G. ;
Trifilo, Matthew J. ;
Edelmann, Kurt H. ;
Teyton, Luc ;
McGavern, Dorian B. ;
Oldstone, Michael B. A. .
NATURE MEDICINE, 2006, 12 (11) :1301-1309
[5]   Regulation of mucosal immune responses by recombinant interleukin 10 produced by intestinal epithelial cells in mice [J].
De Winter, H ;
Elewaut, D ;
Turovskaya, O ;
Huflejt, M ;
Shimeld, C ;
Hagenbaugh, A ;
Binder, S ;
Takahashi, I ;
Kronenberg, M ;
Cheroutre, H .
GASTROENTEROLOGY, 2002, 122 (07) :1829-1841
[6]   Immunostimulatory Tim-1-specific antibody deprograms Tregs and prevents transplant tolerance in mice [J].
Degauque, Nicolas ;
Mariat, Christophe ;
Kenny, James ;
Zhang, Dong ;
Gao, Wenda ;
Vu, Minh Diem ;
Alexopoulos, Sophoclis ;
Oukka, Mohammed ;
Umetsu, Dale T. ;
DeKruyff, Rosemarie H. ;
Kuchroo, Vijay ;
Zheng, Xin Xiao ;
Strom, Terry B. .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (02) :735-741
[7]   Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses [J].
Denning, Timothy L. ;
Wang, Yi-Chong ;
Patel, Seema R. ;
Williams, Ifor R. ;
Pulendran, Bali .
NATURE IMMUNOLOGY, 2007, 8 (10) :1086-1094
[8]   The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain [J].
Donnelly, RP ;
Sheikh, F ;
Kotenko, SV ;
Dickensheets, H .
JOURNAL OF LEUKOCYTE BIOLOGY, 2004, 76 (02) :314-321
[9]   T cells that cannot respond to TGF-β escape control by CD4+CD25+ regulatory T cells [J].
Fahlén, L ;
Read, S ;
Gorelik, L ;
Hurst, SD ;
Coffman, RL ;
Flavell, RA ;
Powrie, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (05) :737-746
[10]   Regulatory T cell lineage specification by the forkhead transcription factor FoxP3 [J].
Fontenot, JD ;
Rasmussen, JP ;
Williams, LM ;
Dooley, JL ;
Farr, AG ;
Rudensky, AY .
IMMUNITY, 2005, 22 (03) :329-341