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

M. A. Forrester, L. Robertson, N. Bayoumi, B. D. Keavney, R. N. Barker, M. A. Vickers

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Although it is widely believed that IL-27 is anti-inflammatory, its role in controlling human immune responses is not fully established. In particular, its interactions with Th17 cytokines are unclear. Our aims were to establish the relationships between IL-27 and pro-inflammatory 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 pro-inflammatory 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.

Original languageEnglish
Pages (from-to)373-383
Number of pages11
JournalClinical and Experimental Immunology
Volume178
Issue number2
Early online date1 Oct 2014
DOIs
Publication statusPublished - Nov 2014

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Keywords

  • cytokines
  • human
  • IL-17A
  • IL-27
  • T cells

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