期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 46, 期 6, 页码 1343-1350出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201546095
关键词
Autoimmunity; IL-12; IL-23p19; IL-27/IL-35Ebi3; IL-39; Inflammation; Systemic lupus erythematosus
类别
资金
- National Basic Research Program 973 Grants [2013CB530506, 2015CB553704]
- National Nature and Science Fund [81471529, 81401332, 81272320, 81471540, 81472647]
- Beijing Natural Science Foundation [7141007]
- Service Industry Scientific Research of National Health and Family Planning Commission of China [2015SQ00192]
- Division of Intramural Research National Eye Institute, National Institutes of Health [EY000262-19, EY000372-14]
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.
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