title: Novel anti-inflammatory interleukin-35 as an emerging target for antiatherosclerotic therapy.
abstract: Atherosclerosis has been widely recognized as a slow progressing inflammatory disease of the aorta and other large caliber arterial vessels. Accumulating evidence suggest that interleukin (IL)-35 can represent an attractive target for future anti-atherosclerotic therapy due to several atheroprotective properties. First, immunosuppressive and anti-inflammatory activity of this cytokine could be beneficial against vascular inflammation. Second, IL-35 can suppress a variety of T cells including proinflammatory Th1 and Th17 cells and probably dendritic cells. Third, IL-35 supports proliferation of regulatory T cells (Tregs), increases their inhibitory function, and induces a new set of Tregs called inducible IL-35-producing Tregs (iTr35 cells). Fourth, this cytokine promotes production of antiinflammatory cytokines such as IL-10 and down-regulates expression of proinflammatory cytokines such as IL-17. Finally, IL-35 is inducible. The fact that IL-35 could be induced by simple compounds such as chemical chaperons may provide advances in developing new efficient strategies for treatment of atherosclerosis. However, it is necessary to test IL-35-inducing factors in order to understand mechanisms of induction and then select the most optimal one. Probably, constructing of humanized antibodies that mimic IL-35 function may provide benefits for advanced atheroprotective therapy.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
authors.forename: Igor A
authors.initials: IA
authors.lastname: Sobenin
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Orekhov
authors.affiliation: Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia. y.bobryshev@unsw.edu.au.
authors.forename: Dimitry A
authors.initials: DA
authors.lastname: Chistiakov
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053712:Interleukin-12 Receptor beta 2 Subunit / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism*; D018448:Models, Immunological; D058990:Molecular Targeted Therapy / Q000379:methods*; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D053712:Interleukin-12 Receptor beta 2 Subunit; D007378:Interleukins; C532417:interleukin-35, human