Linnan Zhu
Hongling Tian
Hai-Xi Sun
Ruoyu Wang
Lianfeng Zhang
Yong Zhao
1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, China;
2 Department of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China;
3 Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Funds: The authors thank Dr. Lianjun Zhang for his reading the manuscript, Mrs. Qing Meng, Mrs. Xiaoqiu Liu, and Mr. Yabing Liu for their expert technical assistance, Mrs. Ling Li for her excellent laboratory management. This work was supported by grants from the National Natural Science Foundation for General and Key Programs (C81530049, C81130055, C31470860, Y.Z.), Knowledge Innovation Program of Chinese Academy of Sciences (XDA04020202-19, Y.Z.), and the CAS/SAFEA International Partnership Program for Creative Research Teams (Y.Z.).
Received Date: 2017-09-16
Rev Recd Date:2017-12-12
Abstract
Abstract
Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1-and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-γ. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway. T-bet mediates the IFN-γ production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.Keywords: interferon-gamma,
interleukin-17,
interleukin-23,
imiquimod-induced psoriasis,
macrophage polarization
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