IL-35 and Autoimmunity: a Comprehensive Perspective

Abstract

Interleukin 35 (IL-35) is the most recently identified member of the IL-12 family of cytokines and offers the potential to be a target for new therapies for autoimmune, inflammatory, and infectious diseases. Similar to other members of the IL-12 family including IL-12, IL-23, and IL-27, IL-35 is composed of a heterodimer of α and β chains, which in the case of IL-35 are the p35 and Epstein-Barr virus-induced gene 3 (EBI3) proteins. However, unlike its proinflammatory relatives, IL-35 has immunosuppressive effects that are mediated through regulatory T and B cells. Although there are limited data available regarding the role of IL-35 in human autoimmunity, several murine models of autoimmunity suggest that IL-35 may have potent effects in regulating immunoreactivity via IL-10-dependent mechanisms. We suggest that similar effects are operational in human disease and IL-35-directed therapies hold significant promise. In particular, we emphasize that IL-35 has immunosuppressive ability that are mediated via regulatory T and B cells that are IL-10 dependent. Further, although deletion of IL-35 does not result in spontaneous breach of tolerance, recombinant IL-35 can improve autoimmune responses in several experimental models.

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

“…IL-35 is a heterodimeric cytokine belonging to the IL-12 family together with IL-12, IL-23, IL-27 and IL-35 [91]. In T cells, IL-35 signals through IL-12Rβ2 and gp130, although it can also signal through IL-12Rβ2/IL-12Rβ2 and gp130/gp130 homodimers [92].…”

Interleukin-35 Inhibits Endothelial Cell Activation by Suppressing MAPK-AP-1 Pathway

“…It shares the IL-12␣ subunit with IL-12, and shares the EBI3 subunit with IL-27. IL-35 is secreted by Tregs, regulatory B cells (Bregs) (11), dendritic cells (12), and to a lesser extent, by endothelial cells, smooth muscle cells, and monocytes (13). It can suppress sev-eral types of chronic inflammatory diseases such as inflammatory bowel disease (14 -16).…”

Análise da expressão gênica do FOXP3, MIP-3? e Interleucinas 2, 10 e 35 em pacientes com ulceração aftosa recorrente

“…A IL-10 e IL-35, são citocinas anti-inflamatórias produzidas pelos Treg (Cakman et al, 1996;Bazrafshani et al, 2003;Liu et al, 2006;Bardel et al, 2008;Choi et al, 2015) e também apresentam expressão gênica aumentada nas amostras de UAR no presente estudo em relação à mucosa oral sadia. Esta associação é positivamente correlacionada ao achado anterior de aumento da expressão gênica do FOXP3, numa provável tentativa de conter o processo inflamatório exacerbado.…”

“…Esta citocina apresenta características imunossupressoras pertencente à família da IL-12, é uma citocina que contribui para a resposta inflamatória em numerosos processos fisiológicos e patológicos (Ning-Wei, 2010;Choi et al, 2015). A IL-12 é composta de duas subunidades, a p35 e a p40, com características pró-inflamatórias, promotora de imunidade mediada por células do tipo Th1 (Brombacher et al 2003).…”

“…IL-35 apresenta características imunossupressivas que são reguladas por células T e B regulatórias IL-10 dependentes (Choi et al, 2015). …”