Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress

Immunoglobulin (Ig), a characteristic marker of B cells, is a multifunctional evolutionary conserved antibody critical for maintaining tissue homeostasis and developing fully protective humoral responses to pathogens. Increasing evidence revealed that Ig is widely expressed in non-immune cells; more...

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Autores principales:	Xiaoting Gong, Huige Yan, Junfan Ma, Zhu Zhu, Shenghua Zhang, Weiyan Xu, Jing Huang, Xiaoyan Qiu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	macrophage IgM Bip inflammatory response ER stress Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/775a17288736407e999088cec69c1129
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spelling	oai:doaj.org-article:775a17288736407e999088cec69c11292021-11-25T17:07:29ZMacrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress10.3390/cells101128122073-4409https://doaj.org/article/775a17288736407e999088cec69c11292021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2812https://doaj.org/toc/2073-4409Immunoglobulin (Ig), a characteristic marker of B cells, is a multifunctional evolutionary conserved antibody critical for maintaining tissue homeostasis and developing fully protective humoral responses to pathogens. Increasing evidence revealed that Ig is widely expressed in non-immune cells; moreover, Ig produced by different lineages cells plays different biological roles. Recently, it has been reported that monocytes or macrophages also express Ig. However, its function remains unclear. In this study, we further identified that Ig, especially Ig mu heavy chain (IgM), was mainly expressed in mice macrophages. We also analyzed the IgM repertoire characteristic in macrophages and found that the V<sub>H</sub>DJ<sub>H</sub> rearrangements of macrophage-derived IgM showed a restricted and conservative V<sub>H</sub>DJ<sub>H</sub> pattern, which differed from the diverse V<sub>H</sub>DJ<sub>H</sub> rearrangement pattern of the B cell-expressed IgM in an individual. Functional investigation showed that IgM knockdown significantly promoted macrophage migration and FAK/Src-Akt axis activation. Furthermore, some inflammatory cytokines such as MCP1 and IL-6 increased after IgM knockdown under LPS stimulation. A mechanism study revealed that the IgM interacted with binding immunoglobulin protein (Bip) and inhibited inflammatory response and unfolded protein response (UPR) activation in macrophages. Our data elucidate a previously unknown function of IgM in macrophages that explains its ability to act as a novel regulator of Bip to participate in endoplasmic reticulum stress and further regulate the inflammatory response.Xiaoting GongHuige YanJunfan MaZhu ZhuShenghua ZhangWeiyan XuJing HuangXiaoyan QiuMDPI AGarticlemacrophageIgMBipinflammatory responseER stressBiology (General)QH301-705.5ENCells, Vol 10, Iss 2812, p 2812 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	macrophage IgM Bip inflammatory response ER stress Biology (General) QH301-705.5
spellingShingle	macrophage IgM Bip inflammatory response ER stress Biology (General) QH301-705.5 Xiaoting Gong Huige Yan Junfan Ma Zhu Zhu Shenghua Zhang Weiyan Xu Jing Huang Xiaoyan Qiu Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress
description	Immunoglobulin (Ig), a characteristic marker of B cells, is a multifunctional evolutionary conserved antibody critical for maintaining tissue homeostasis and developing fully protective humoral responses to pathogens. Increasing evidence revealed that Ig is widely expressed in non-immune cells; moreover, Ig produced by different lineages cells plays different biological roles. Recently, it has been reported that monocytes or macrophages also express Ig. However, its function remains unclear. In this study, we further identified that Ig, especially Ig mu heavy chain (IgM), was mainly expressed in mice macrophages. We also analyzed the IgM repertoire characteristic in macrophages and found that the V<sub>H</sub>DJ<sub>H</sub> rearrangements of macrophage-derived IgM showed a restricted and conservative V<sub>H</sub>DJ<sub>H</sub> pattern, which differed from the diverse V<sub>H</sub>DJ<sub>H</sub> rearrangement pattern of the B cell-expressed IgM in an individual. Functional investigation showed that IgM knockdown significantly promoted macrophage migration and FAK/Src-Akt axis activation. Furthermore, some inflammatory cytokines such as MCP1 and IL-6 increased after IgM knockdown under LPS stimulation. A mechanism study revealed that the IgM interacted with binding immunoglobulin protein (Bip) and inhibited inflammatory response and unfolded protein response (UPR) activation in macrophages. Our data elucidate a previously unknown function of IgM in macrophages that explains its ability to act as a novel regulator of Bip to participate in endoplasmic reticulum stress and further regulate the inflammatory response.
format	article
author	Xiaoting Gong Huige Yan Junfan Ma Zhu Zhu Shenghua Zhang Weiyan Xu Jing Huang Xiaoyan Qiu
author_facet	Xiaoting Gong Huige Yan Junfan Ma Zhu Zhu Shenghua Zhang Weiyan Xu Jing Huang Xiaoyan Qiu
author_sort	Xiaoting Gong
title	Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress
title_short	Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress
title_full	Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress
title_fullStr	Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress
title_full_unstemmed	Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress
title_sort	macrophage-derived immunoglobulin m inhibits inflammatory responses via modulating endoplasmic reticulum stress
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/775a17288736407e999088cec69c1129
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Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress

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