Interleukin-35 in immune-related diseases: protection or destruction

Junfeng Zhang, Yunsheng Zhang, Qingpeng Wang, Chunlei Li, Hongxin Deng, Chuanping Si, Huabao Xiong

Research output: Contribution to journalReview articlepeer-review

70 Scopus citations

Abstract

Interleukin-35 (IL-35) is a recently identified heterodimeric cytokine in the IL-12 family. It consists of an IL-12 subunit α chain (P35) and IL-27 subunit Epstein–Barr virus-induced gene 3 (EBI3) β chain. Unlike the other IL-12 family members, it signals through four unconventional receptors: IL-12Rβ2–IL-27Rα, IL-12Rβ2–IL-12Rβ2, IL-12Rβ2–GP130, and GP130–GP130. Interleukin-35 signaling is mainly carried out through the signal transducer and activator of transcription family of proteins. It is secreted not only by regulatory T (Treg) cells, but also by CD8 + Treg cells, activated dendritic cells and regulatory B cells. It exhibits immunosuppressive functions distinct from those of other members of the IL-12 family; these are mediated primarily by the inhibition of T helper type 17 cell differentiation and promotion of Treg cell proliferation. Interleukin-35 plays a critical role in several immune-associated diseases, such as autoimmune diseases and viral and bacterial infections, as well as in tumors. In this review, we summarize the structure and function of IL-35, describe its role in immune-related disorders, and discuss the mechanisms by which it regulates the development and progression of diseases, including inflammatory bowel disease, collagen-induced arthritis, allergic airway disease, hepatitis, and tumors. The recent research on IL-35, combined with improved techniques of studying receptors and signal transduction pathways, allows for consideration of IL-35 as a novel immunotherapy target.

Original languageEnglish
Pages (from-to)13-20
Number of pages8
JournalImmunology
Volume157
Issue number1
DOIs
StatePublished - May 2019

Keywords

  • immune-related diseases
  • immunosuppression
  • interleukin-35
  • regulatory T cells

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