title: IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines.
abstract: It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies.
authors.affiliation: Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Li
authors.forename: Jietang
authors.initials: J
authors.lastname: Mai
authors.forename: Anthony
authors.initials: A
authors.lastname: Virtue
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Ren
authors.initials: R
authors.lastname: Gong
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Sha
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gutchigian
authors.forename: Andrew
authors.initials: A
authors.lastname: Frisch
authors.forename: Imani
authors.initials: I
authors.lastname: Hodge
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000145:classification / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007378:Interleukins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D018448:Models, Immunological; D011401:Promoter Regions, Genetic; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D016207:Cytokines; D007378:Interleukins; D035683:MicroRNAs; D021122:Protein Subunits; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C532417:interleukin-35, human; C569375:interleukin-35, mouse