Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10.
Interleukin 10 (IL-10) has a prominent function in regulating the balance between protective and pathological T cell responses. Consistent with that activity, many sources of this cytokine are found in vivo, including from myeloid cells and a variety of T cell subsets. However, although there are many pathways that regulate innate production of IL-10, the factors that govern its synthesis by the adaptive response are poorly understood. Here we report that IL-27 and IL-6 induced T helper type 1 and type 2 cells, as well as T helper cells that produce IL-17, to secrete IL-10. This effect was dependent on the transcription factors STAT1 and STAT3 for IL-27 and on STAT3 for IL-6. Our studies identify a previously unknown pathway that allows the immune system to temper inflammatory responses.
Stumhofer
Jason S
JS
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. chunter@vet.upenn.edu
Silver
Jonathan S
JS
Laurence
Arian
A
Porrett
Paige M
PM
Harris
Tajie H
TH
Turka
Laurence A
LA
Ernst
Matthias
M
Saris
Christiaan J M
CJ
O'Shea
John J
JJ
Hunter
Christopher A
CA
D000818:Animals; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer
D020381:Interleukin-17; D015850:Interleukin-6; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; D016753:Interleukin-10