Human interleukin-27: wide individual variation in plasma levels and complex inter-relationships with interleukin-17A

被引:7
作者
Forrester, M. A. [1 ]
Robertson, L. [1 ]
Bayoumi, N. [4 ]
Keavney, B. D. [3 ]
Barker, R. N. [1 ]
Vickers, M. A. [2 ]
机构
[1] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
[2] Univ Aberdeen, Acad Transfus Med Unit, Aberdeen AB25 2ZD, Scotland
[3] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[4] King Saud Univ, Coll Med, Dept Physiol, Riyadh 11461, Saudi Arabia
关键词
cytokines; human; IL-17A; IL-27; T cells; T-CELL; IL-17; PRODUCTION; DISEASE-ACTIVITY; VIRUS INFECTION; CUTTING EDGE; IL-27; SERUM; EXPRESSION; WSX-1; SUPPRESSION;
D O I
10.1111/cei.12408
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although it is widely believed that interleukin (IL)-27 is anti-inflammatory, its role in controlling human immune responses is not fully established. In particular, its interactions with T helper type 17 (Th) 17 cytokines are unclear. Our aims were to establish the relationships between IL-27 and proinflammatory cytokines, including IL-17A, in human sera and cultures of peripheral blood mononuclear cells. Plasma IL-27 levels in 879 healthy humans from 163 families varied widely, but with relatively low heritability (19%). Despite IL-27 including a subunit encoded by Epstein-Barr virus-induced gene 3 (EBI3), there was no correlation of levels with serological evidence of infection with the virus. Although IL-27 has been reported to inhibit IL-17A production, we demonstrated a strong positive correlation in sera, but lower correlations of IL-27 with other proinflammatory cytokines. We verified that IL-27 inhibited IL-17A production by human peripheral blood T cells in vitro, but not that it stimulated IL-10 secretion. Importantly, addition of IL-17A decreased IL-27 production by stimulated T cells but had the opposite effect on resting T cells. Together, these data suggest a model whereby IL-27 and IL-17A exerts complex reciprocal effects to boost inflammatory responses, but restrain resting cells to prevent inappropriate activation.
引用
收藏
页码:373 / 383
页数:11
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