title: 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.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, Davis, CA, 95616, USA.|Division of Rheumatology, CHA University Medical Center, Bundang, 463-712, Korea.
authors.forename: Jinjung
authors.initials: J
authors.lastname: Choi
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, Davis, CA, 95616, USA.
authors.forename: Patrick S C
authors.initials: PS
authors.lastname: Leung
authors.affiliation: Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bowlus
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, Davis, CA, 95616, USA. megershwin@ucdavis.edu.
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D015551:Autoimmunity; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D056747:Immunomodulation; D018664:Interleukin-12 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D051379:Mice; D058990:Molecular Targeted Therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D007378:Interleukins; C532417:interleukin-35, human; D018664:Interleukin-12
keywords: Autoimmunity; IL-12; Immunosuppressants; Regulatory T cells