A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses.
CD4+ helper T (TH) cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed TH(IL-17), TH17 or inflammatory TH (THi), has been identified as critical mediators of tissue inflammation. These cells produce IL-17 (also called IL-17A) and IL-17F, two most homologous cytokines sharing similar regulations. Here we report that when overexpressed in 293T cells, IL-17 and IL-17F form not only homodimers but also heterodimers, which we name as IL-17A/F. Fully differentiated mouse THi cells also naturally secrete IL-17A/F as well as IL-17 and IL-17F homodimeric cytokines. Recombinant IL-17A/F protein exhibits intermediate levels of potency in inducing IL-6 and KC (CXCL1) as compared to homodimeric cytokines. IL-17A/F regulation of IL-6 and KC expression is dependent on IL-17RA and TRAF6. Thus, IL-17A/F cytokine represents another mechanism whereby T cells regulate inflammatory responses and may serve as a novel target for treating various immune-mediated diseases.
Chang
Seon Hee
SH
Department of Immunology, MD Anderson Cancer Center, 7455 Fannin, Unit 906, Houston, TX 77030, USA.
Dong
Chen
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D019281:Dimerization; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D020381:Interleukin-17 / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000378:metabolism
C098680:Il17a protein, mouse; C515932:Il17f protein, mouse; D020381:Interleukin-17; D011993:Recombinant Fusion Proteins