title: IL-27 suppresses the production of IL-22 in human CD4(+) T cells by inducing the expression of SOCS1.
abstract: IL-27, a member of IL-6/IL-12 cytokine family, plays pro- and anti-inflammatory functions in immune responses. It can promote inflammation by inducing Th1 differentiation and exert the inhibitory effects on Th2 and Th17 mediated immune responses. Moreover, IL-27 suppresses CD28-mediated IL-2 production from mouse naive CD4(+) T cells. In the present study, we demonstrate that IL-27 inhibits the production of IL-22 and induces the expression of IFN-γ in CD4(+) T cells from human umbilical cord blood mononuclear cells (CBMCs) stimulated with anti-CD3 and anti-CD28 in dose-dependent manner. In addition, the suppression of IL-22 is not dependent on the production of IFN-γ and IL-10. Importantly, IL-27 promotes the expression of SOCS1, which could be inhibited by a Jak2/STAT inhibitor, AG490. Importantly, the expression of IL-22 could not be inhibited under the circumstances with the lower expression of SOCS1. Moreover, IL-27 inhibits the production of IL-22 in CD4(+)CD45RA(+) and CD4(+)CD45RO(+) T cells from PBMCs. These data identify that IL-27 may suppress the production of IL-22 by inducing the expression of SOCS1 in human CD4(+) T cells. Furthermore, it demonstrates that IL-27 may be a therapeutic approach in the treatment of IL-22-mediated diseases.
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine, Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Zitao
authors.initials: Z
authors.lastname: Li
authors.forename: Binyan
authors.initials: B
authors.lastname: Yang
authors.forename: Sifei
authors.initials: S
authors.lastname: Yu
authors.forename: Changyou
authors.initials: C
authors.lastname: Wu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis* / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D016753:Interleukin-10; D007378:Interleukins; D017493:Leukocyte Common Antigens; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D020032:Tyrphostins; D000097043:Interleukin-22; C464565:MYDGF protein, human; C108944:SOCS1 protein, human; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
keywords: CD4(+) T cells; Interleukin-22; Interleukin-27; SOCS1