ORIGINAL ARTICLE

Cell Research (2007): 435-440
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A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses

Seon Hee Chang¹ and Chen Dong¹

Correspondence: Chen Dong Tel: +1-713-563-3203; Fax: +1-713-563-0604 E-mail: cdong@mdanderson.org

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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.

Cell Research (2007) 17:435–440. doi: 10.1038/cr.2007.35; published online 24 April 2007

Keywords: inflammation, IL-17, T cells