A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells.
Regulatory T cells (T(reg) cells) expressing the transcription factor Foxp3 are key in maintaining the balance of immune homeostasis. However, distinct induced T regulatory type 1 (Tr1) cells that lack Foxp3 expression also regulate T cell function, mainly by producing the immunosuppressive cytokine interleukin 10 (IL-10). However, the factors required for the induction of IL-10-producing suppressive T cells are not fully understood. Here we demonstrate that dendritic cells modified by T(reg) cells induced the generation of IL-10-producing Tr1 cells. The differentiation of naive CD4+ T cells into IL-10-producing cells was mediated by IL-27 produced by the T(reg) cell-modified dendritic cells, and transforming growth factor-beta amplified the generation of induced IL-10+ Tr1 cells by IL-27. Thus, IL-27 and transforming growth factor-beta promote the generation of IL-10-producing Tr1 cells.
Awasthi
Amit
A
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA.
Carrier
Yijun
Y
Peron
Jean P S
JP
Bettelli
Estelle
E
Kamanaka
Masahito
M
Flavell
Richard A
RA
Kuchroo
Vijay K
VK
Oukka
Mohamed
M
Weiner
Howard L
HL
D000818:Animals; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000502:physiology*; D020381:Interleukin-17 / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D020381:Interleukin-17; D016212:Transforming Growth Factor beta; D016753:Interleukin-10