Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells.
Excessive inflammation occurs during infection and autoimmunity in mice lacking the alpha-subunit of the interleukin 27 (IL-27) receptor. The molecular mechanisms underlying this increased inflammation are incompletely understood. Here we report that IL-27 upregulated IL-10 in effector T cells that produced interferon-gamma and expressed the transcription factor T-bet but did not express the transcription factor Foxp3. These IFN-gamma+T-bet+Foxp3- cells resembled effector T cells that have been identified as the main source of host-protective IL-10 during inflammation. IL-27-induced production of IL-10 was associated with less secretion of IL-17, and exogenous IL-27 reduced the severity of adoptively transferred experimental autoimmune encephalomyelitis by a mechanism dependent on IL-10. Our data show that IL-27-induced production of IL-10 by effector T cells contributes to the immunomodulatory function of IL-27.
Fitzgerald
Denise C
DC
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Zhang
Guang-Xian
GX
El-Behi
Mohamed
M
Fonseca-Kelly
Zoë
Z
Li
Hongmei
H
Yu
Shuo
S
Saris
Christiaan J M
CJ
Gran
Bruno
B
Ciric
Bogoljub
B
Rostami
Abdolmohamad
A
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D002493:Central Nervous System Diseases / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D020381:Interleukin-17; D016753:Interleukin-10