Research Papers: Immunology:

IL-33/ST2-mediated inflammation in macrophages is directly abrogated by IL-10 during rheumatoid arthritis

Si Chen, Bingni Chen, Zhongyang Wen, Zhong Huang and Liang Ye _

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Oncotarget. 2017; 8:32407-32418. https://doi.org/10.18632/oncotarget.16299

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Si Chen1,2,*, Bingni Chen1,2,3,*, Zhongyang Wen1,2,3,*, Zhong Huang1,2,3 and Liang Ye1,2,3

1 Institute of Biological Therapy, Shenzhen University, Shenzhen, China

2 Department of Pathogen Biology and Immunology, Shenzhen University School of Medicine, Shenzhen, China

3 Shenzhen City Shenzhen University Immunodiagnostic Technology Platform, Shenzhen, China

* These authors have contributed equally to this work

Correspondence to:

Liang Ye, email:

Zhong Huang, email:

Keywords: IL-33, IL-33 receptor, IL-10, macrophage, rheumatoid arthritis, Immunology and Microbiology Section, Immune response, Immunity

Received: August 11, 2016 Accepted: March 01, 2017 Published: March 16, 2017


IL-10 is an immunosuppressive cytokine produced and sensed by many immune cells and exerts a protective role in autoimmune diseases. However, the underlying mechanism by which IL-10 contributes to prevent the arthritic inflammation in macrophages is poorly understood. Herein we report on a novel anti-arthritic property of IL-10 through the inhibition of IL-33 signaling by macrophages during collagen-induced arthritis (CIA) development. We show that IL-33 expression rather than its receptor (ST2) is positively correlated with IL-10 level in active RA. IL-10 deficiency in mice leads to significant upregulation of IL-33 expression and aggravates the progression of CIA, while exogenous IL-10 treatment effectively diminishes IL-33 production in IL-10 knockout (IL-10-/-) CIA mice. We demonstrate further that the inhibitory effect of IL-10 in suppressing IL-33 production requires STAT3 activation in macrophages. Furthermore, IL-33 stimulated proinflammatory genes are notably increased in IL-10-/- CIA mice, whereas macrophages treated with recombinant IL-10 exhibit decreased IL-33 amplified inflammation and inhibited IL-33 activated NF-κB signaling pathway. Our findings indicate that IL-10 act as a negative regulator of IL-33/ST2 signaling pathways in vivo, suggesting a potential therapeutic role of IL-10 in autoimmune diseases.

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