Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway

Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway

The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and Ah...

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Main Authors: Junyu Zhu, Li Luo, Lixing Tian, Shangqi Yin, Xiaoyuan Ma, Shaowen Cheng, Wanqi Tang, Jing Yu, Wei Ma, Xiaoying Zhou, Xia Fan, Xue Yang, Jun Yan, Xiang Xu, Chuanzhu Lv, Huaping Liang
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-09-01
Series:Frontiers in Immunology
Subjects:
aryl hydrocarbon receptor
IL-10
macrophages
inflammation
signal transduction
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.02033/full
id doaj-f621e5394a094a9cadcde7688b11328d
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Junyu Zhu
Li Luo
Lixing Tian
Shangqi Yin
Xiaoyuan Ma
Xiaoyuan Ma
Shaowen Cheng
Wanqi Tang
Jing Yu
Wei Ma
Xiaoying Zhou
Xia Fan
Xue Yang
Jun Yan
Xiang Xu
Chuanzhu Lv
Huaping Liang
spellingShingle Junyu Zhu
Li Luo
Lixing Tian
Shangqi Yin
Xiaoyuan Ma
Xiaoyuan Ma
Shaowen Cheng
Wanqi Tang
Jing Yu
Wei Ma
Xiaoying Zhou
Xia Fan
Xue Yang
Jun Yan
Xiang Xu
Chuanzhu Lv
Huaping Liang
Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway
Frontiers in Immunology
aryl hydrocarbon receptor
IL-10
macrophages
inflammation
signal transduction
author_facet Junyu Zhu
Li Luo
Lixing Tian
Shangqi Yin
Xiaoyuan Ma
Xiaoyuan Ma
Shaowen Cheng
Wanqi Tang
Jing Yu
Wei Ma
Xiaoying Zhou
Xia Fan
Xue Yang
Jun Yan
Xiang Xu
Chuanzhu Lv
Huaping Liang
author_sort Junyu Zhu
title Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway
title_short Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway
title_full Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway
title_fullStr Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway
title_full_unstemmed Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway
title_sort aryl hydrocarbon receptor promotes il-10 expression in inflammatory macrophages through src-stat3 signaling pathway
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2018-09-01
description The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-κB pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR-overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10 expression by inflammatory macrophages. Adoptive transfer of AhR-expressing macrophages protected mice against LPS-induced peritonitis associated with high IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling pathway as a critical pathway in the immune regulation of inflammatory macrophages, It suggests that AhR may be a potential therapeutic target in immune response.
topic aryl hydrocarbon receptor
IL-10
macrophages
inflammation
signal transduction
url https://www.frontiersin.org/article/10.3389/fimmu.2018.02033/full
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spelling doaj-f621e5394a094a9cadcde7688b11328d2020-11-25T00:20:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-09-01910.3389/fimmu.2018.02033407242Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling PathwayJunyu Zhu0Li Luo1Lixing Tian2Shangqi Yin3Xiaoyuan Ma4Xiaoyuan Ma5Shaowen Cheng6Wanqi Tang7Jing Yu8Wei Ma9Xiaoying Zhou10Xia Fan11Xue Yang12Jun Yan13Xiang Xu14Chuanzhu Lv15Huaping Liang16State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaEmergency and Trauma College of Hainan Medical University, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaTrauma Center, First Affiliated Hospital of Hainan Medical University, Haikou, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaEmergency and Trauma College of Hainan Medical University, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, ChinaThe aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-κB pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR-overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10 expression by inflammatory macrophages. Adoptive transfer of AhR-expressing macrophages protected mice against LPS-induced peritonitis associated with high IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling pathway as a critical pathway in the immune regulation of inflammatory macrophages, It suggests that AhR may be a potential therapeutic target in immune response.https://www.frontiersin.org/article/10.3389/fimmu.2018.02033/fullaryl hydrocarbon receptorIL-10macrophagesinflammationsignal transduction

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