Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis.
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.
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Masako
M
Murai
Olga
O
Turovskaya
Gisen
G
Kim
Rajat
R
Madan
Christopher L
CL
Karp
Hilde
H
Cheroutre
Mitchell
M
Kronenberg
D019264:Adoptive Transfer; D000818:Animals; D018845:CD11 Antigens / Q000276:immunology; D003092:Colitis / Q000276:immunology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D018845:CD11 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10