TY - JOUR
T1 - Interleukin-35 in immune-related diseases
T2 - protection or destruction
AU - Zhang, Junfeng
AU - Zhang, Yunsheng
AU - Wang, Qingpeng
AU - Li, Chunlei
AU - Deng, Hongxin
AU - Si, Chuanping
AU - Xiong, Huabao
N1 - Publisher Copyright:
© 2019 John Wiley & Sons Ltd
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - immune-related diseases
KW - immunosuppression
KW - interleukin-35
KW - regulatory T cells
UR - http://www.scopus.com/inward/record.url?scp=85062711002&partnerID=8YFLogxK
U2 - 10.1111/imm.13044
DO - 10.1111/imm.13044
M3 - Review article
C2 - 30681737
AN - SCOPUS:85062711002
SN - 0019-2805
VL - 157
SP - 13
EP - 20
JO - Immunology
JF - Immunology
IS - 1
ER -