IL-35 is a novel responsive anti-inflammatory cytokine - a new system of categorizing anti-inflammatory cytokines

Xinyuan Li, Jietang Mai, Anthony Virtue, Ying Yin, Ren Gong, Xiaojin Sha, Stefanie Gutchigian, Andrew Frisch, Imani Hodge, Xiaohua Jiang, Hong Wang, Xiao Feng Yang

Research output: Contribution to journalArticlepeer-review

215 Scopus citations

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.

Original languageEnglish
Article numbere33628
JournalPLoS ONE
Volume7
Issue number3
DOIs
StatePublished - Mar 16 2012
Externally publishedYes

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