Interleukin 35 (IL-35) is an IL-12 family cytokine produced by regulatory, but not effector, T-cells and plays a role in immune suppression. It is a dimeric protein composed of IL-12α and IL-27β chains, which are encoded by two separate genes called IL12A and EBI3, respectively. Secreted by regulatory T-cells (Tregs), IL-35 suppresses inflammatory responses of immune cells. IL-35 is not constitutively expressed in tissues, but the gene encoding IL-35 is transcribed by vascular endothelial cells, smooth muscle cells and monocytes after activation with proinflammatory stimuli.
Studies in mice show the absence of either IL-35 chain from regulatory Tregs reduces the cells' ability to suppress inflammation; this has been observed during cell culture experiments and using an experimental model for inflammatory bowel disease. To produce its suppressive effects (eg on collagen-induced arthritis), IL-35 has selective activities on different T-cell subsets; it induces proliferation of Treg cell populations but reduces activity of Th17 cell populations.
- Li X, Mai J, Virtue A, et al. (March 2012). "IL-35 is a novel responsive anti-inflammatory cytokine—a new system of categorizing anti-inflammatory cytokines". PLoS ONE. 7 (3): e33628. PMC . PMID 22438968. doi:10.1371/journal.pone.0033628.
- Collison LW, Workman CJ, Kuo TT, et al. (November 2007). "The inhibitory cytokine IL-35 contributes to regulatory T-cell function". Nature. 450 (7169): 566–9. PMID 18033300. doi:10.1038/nature06306.
- Niedbala W, Wei XQ, Cai B, et al. (November 2007). "IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells". Eur. J. Immunol. 37 (11): 3021–9. PMID 17874423. doi:10.1002/eji.200737810.