Journal Article

IL-35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines

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

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alternative Splicing / Analysis / Animals / Anti-inflammatory agents / Arthritis / Autoimmune diseases / Base Sequence / Biology / Bone morphogenetic proteins / Confidence intervals / Cytokines / Cytokines - classification / Cytokines - genetics / Cytokines - immunology / DNA Methylation / Gastroenterology / Gene Expression / Genomes / Human tissues / Humans / Immune Tolerance - immunology / Immunosuppression / Immunotherapy / Inflammation / Inflammation - immunology / Inflammation - prevention & control / Inflammatory bowel disease / Interleukin / Interleukin 10 / Interleukins / Interleukins - biosynthesis / Interleukins - chemistry / Interleukins - genetics / Interleukins - immunology / Lymphocytes / Medicine / Mice / Mice, Knockout / MicroRNA / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miRNA / Models, Immunological / Promoter Regions, Genetic / Protein binding / Protein Subunits / Proteins / Regulatory mechanisms (biology) / RNA, Messenger - genetics / RNA, Messenger - metabolism / Rodents / Standard deviation / Statistical analysis / Statistical methods / T-Lymphocytes, Regulatory - immunology / Tissues / Transcription factors / Transforming growth factor / Transforming Growth Factor beta - immunology / Transforming growth factors