A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice

作者:Wang, Xiaoqian; Wei, Yinxiang; Xiao, He; Liu, Xiaoling; Zhang, Yu; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Ma, Ning; Shen, Beifen; Li, Yan; Egwuagu, Charles E.*; Wang, Renxi*
来源:European Journal of Immunology, 2016, 46(6): 1343-1350.
DOI:10.1002/eji.201546095

摘要

Interleukin-12 family cytokines have emerged as critical regulators of immunity with some members (IL-12, IL-23) associated with disease pathogenesis while others (IL-27, IL-35) mitigate autoimmune diseases. Each IL-12 family member is comprised of an alpha and a beta chain, and chain-sharing is a key feature. Although four bona fide members have thus far been described, promiscuous chain-pairing between alpha (IL-23p19, IL-27p28, IL-12/IL-35p35) and beta (IL-12/IL-23p40, IL-27/IL-35Ebi3) subunits, predicts six possible heterodimeric IL-12 family cytokines. Here, we describe a new IL-12member composed of IL-23p19 and Ebi3 heterodimer (IL-39) that is secreted by LPS-stimulated B cells and GL7(+) activated B cells of lupus-like mice. We further show that IL-39 mediates inflammatory responses through activation of STAT1/STAT3 in lupus-like mice. Taken together, our results show that IL-39 might contribute to immunopathogenic mechanisms of systemic lupus erythematosus, and could be used as a possible target for its treatment.