IL-27 is a key regulator of IL-10 and IL-17 production by human CD4+ T cells.
Although the physiologic pathways that control regulatory T cells (Foxp3-expressing regulatory T cells, IL-10-secreting Tr1 cells) and Th17 cells in rodents have been defined, the factors that control these differentiation pathways in humans are not well understood. In this study, we show that IL-27 promotes the differentiation of IL-10-secreting Tr1 cells while inhibiting Th17 generation and molecules associated with Th17 function. Furthermore, IL-27 inhibits IL-17-polarizing cytokines on dendritic cells, which in turn decrease IL-17 secretion from T cells. Our results demonstrate that IL-27 plays a key role in human T cells by promoting IL-10-secreting Tr1 cells and inhibiting Th17 cells and thus provides a dual regulatory mechanism to control autoimmunity and tissue inflammation.
Murugaiyan
Gopal
G
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Mittal
Akanksha
A
Lopez-Diego
Rocio
R
Maier
Lisa M
LM
Anderson
David E
DE
Weiner
Howard L
HL
D001327:Autoimmune Diseases / Q000473:pathology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D025461:Feedback, Physiological / Q000276:immunology; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D006131:Growth Inhibitors; C508609:IL10 protein, human; C508717:IL17A protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D007378:Interleukins; C464565:MYDGF protein, human; D016753:Interleukin-10