Interleukin 35: Critical regulator of immunity and lymphocyte-mediated diseases.
Cytokines coordinate the activities of innate and adaptive immune systems and the Interleukin 12 (IL-12) family of cytokines has emerged as critical regulators of immunity in infectious and autoimmune diseases. While some members (IL-12 and IL-23) are associated with the pathogenesis of chronic inflammatory diseases, others (IL-27 and IL-35) mitigate autoimmune diseases. Unlike IL-12, IL-23 and IL-27 that are produced mainly by antigen presenting cells, IL-35 is predominantly secreted by regulatory B (i35-Bregs) and T (iTR35) cells. The discovery that IL-35 can induce the conversion or expansion of lymphocytes to regulatory B and T cells has considerable implications for therapeutic use of autologous regulatory B and T cells in human diseases. Although our current understanding of the immunobiology of IL-35 or its subunits (p35 and Ebi3) is still rudimentary, our goal in this review is to summarize what we know about this enigmatic cytokine and its potential clinical use, particularly in the treatment of CNS autoimmune diseases.
Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: egwuaguc@nei.nih.gov.
Charles E
CE
Egwuagu
Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Cheng-Rong
CR
Yu
Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Lin
L
Sun
Laboratory of Immunology, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
Renxi
R
Wang
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000473:pathology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D007378:Interleukins; C532417:interleukin-35, human
Adoptive B cell therapy; Autoimmune diseases; Breg; Cytokine therapy; IL-12 family cytokines; Interleukin 35; Regulatory B cells; i35-Breg; iTR35