IL-17 inhibits human Th1 differentiation through IL-12R beta 2 downregulation.
Th17 cells are critical in adaptive immunity and autoimmune disease. The polarized development of Th17, Th1 and Th2 cells is dependent on counterregulatory effects on each other. Whereas IFN-gamma inhibits Th17 development, the effect of IL-17 in human Th1 development is not known. We report a novel negative regulatory role of IL-17 on IL-12R beta 2 expression associated with reduced IL-12 responsiveness. IL-17 decreased IL-12-induced IFN-gamma expression in PBMC and developing Th1 cells, associated with a selective reduction in IL-12R beta 2, and not IL-23R, IL-12R beta 1 or T-bet. Counterregulatory effects of human Th17 on Th1 lineage cytokines may contribute to lineage divergence. In autoimmune disease, IL-17 may reinforce its own developmental programme by reducing IL-12 responsiveness, thus limiting inhibitory effects of IFN-gamma on Th17 development.
Toh
Myew-Ling
ML
Department of Immunology, University of Lyon, Edouard Herriot Hospital, Lyon, France.
Kawashima
Masanori
M
Zrioual
Saloua
S
Hot
Arnaud
A
Miossec
Philippe
P
Miossec
Pierre
P
D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D053712:Interleukin-12 Receptor beta 2 Subunit / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects*
D053712:Interleukin-12 Receptor beta 2 Subunit; D020381:Interleukin-17; D012333:RNA, Messenger