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Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage

C-type lectin Ocilrp2/Clec2i is widely expressed in dendritic cells, lymphokine-activated killer cells and activated T cells. Previous studies have shown that Ocilrp2 is an important regulator in the activation of T cells and NK cells. However, the role of Ocilrp2 in the inflammatory responses by ac...

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Autores principales: Cao, Mingya, Ma, Lina, Yan, Chenyang, Wang, Han, Ran, Mengzhe, Chen, Ying, Wang, Xiao, Liang, Xiaonan, Chai, Lihui, Li, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589251/
https://www.ncbi.nlm.nih.gov/pubmed/36300111
http://dx.doi.org/10.3389/fimmu.2022.984520
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author Cao, Mingya
Ma, Lina
Yan, Chenyang
Wang, Han
Ran, Mengzhe
Chen, Ying
Wang, Xiao
Liang, Xiaonan
Chai, Lihui
Li, Xia
author_facet Cao, Mingya
Ma, Lina
Yan, Chenyang
Wang, Han
Ran, Mengzhe
Chen, Ying
Wang, Xiao
Liang, Xiaonan
Chai, Lihui
Li, Xia
author_sort Cao, Mingya
collection PubMed
description C-type lectin Ocilrp2/Clec2i is widely expressed in dendritic cells, lymphokine-activated killer cells and activated T cells. Previous studies have shown that Ocilrp2 is an important regulator in the activation of T cells and NK cells. However, the role of Ocilrp2 in the inflammatory responses by activated macrophages is currently unknown. This study investigated the expression of inflammatory cytokines in LPS-induced macrophages from primary peritoneal macrophages silenced by specific siRNA target Ocilrp2. Ocilrp2 was significantly downregulated in macrophages via NF-κB and pathways upon LPS stimuli or VSV infection. Silencing Ocilrp2 resulted in the increased expression of IL-6 in LPS-stimulated peritoneal macrophages and mice. Moreover, IL-6 expression was reduced in LPS-induced Ocilrp2 over-expressing iBMDM cells. Furthermore, we found that Ocilrp2-related Syk activation is responsible for expressing inflammatory cytokines in LPS-stimulated macrophages. Silencing Ocilrp2 significantly promotes the binding of Syk to Dap12. Altogether, we identified the Ocilrp2 as a critical role in the TLR4 signaling pathway and inflammatory macrophages’ immune regulation, and added mechanistic insights into the crosstalk between TLR and Syk signaling.
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spelling pubmed-95892512022-10-25 Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage Cao, Mingya Ma, Lina Yan, Chenyang Wang, Han Ran, Mengzhe Chen, Ying Wang, Xiao Liang, Xiaonan Chai, Lihui Li, Xia Front Immunol Immunology C-type lectin Ocilrp2/Clec2i is widely expressed in dendritic cells, lymphokine-activated killer cells and activated T cells. Previous studies have shown that Ocilrp2 is an important regulator in the activation of T cells and NK cells. However, the role of Ocilrp2 in the inflammatory responses by activated macrophages is currently unknown. This study investigated the expression of inflammatory cytokines in LPS-induced macrophages from primary peritoneal macrophages silenced by specific siRNA target Ocilrp2. Ocilrp2 was significantly downregulated in macrophages via NF-κB and pathways upon LPS stimuli or VSV infection. Silencing Ocilrp2 resulted in the increased expression of IL-6 in LPS-stimulated peritoneal macrophages and mice. Moreover, IL-6 expression was reduced in LPS-induced Ocilrp2 over-expressing iBMDM cells. Furthermore, we found that Ocilrp2-related Syk activation is responsible for expressing inflammatory cytokines in LPS-stimulated macrophages. Silencing Ocilrp2 significantly promotes the binding of Syk to Dap12. Altogether, we identified the Ocilrp2 as a critical role in the TLR4 signaling pathway and inflammatory macrophages’ immune regulation, and added mechanistic insights into the crosstalk between TLR and Syk signaling. Frontiers Media S.A. 2022-10-10 /pmc/articles/PMC9589251/ /pubmed/36300111 http://dx.doi.org/10.3389/fimmu.2022.984520 Text en Copyright © 2022 Cao, Ma, Yan, Wang, Ran, Chen, Wang, Liang, Chai and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Cao, Mingya
Ma, Lina
Yan, Chenyang
Wang, Han
Ran, Mengzhe
Chen, Ying
Wang, Xiao
Liang, Xiaonan
Chai, Lihui
Li, Xia
Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage
title Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage
title_full Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage
title_fullStr Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage
title_full_unstemmed Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage
title_short Mouse Ocilrp2/Clec2i negatively regulates LPS-mediated IL-6 production by blocking Dap12-Syk interaction in macrophage
title_sort mouse ocilrp2/clec2i negatively regulates lps-mediated il-6 production by blocking dap12-syk interaction in macrophage
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589251/
https://www.ncbi.nlm.nih.gov/pubmed/36300111
http://dx.doi.org/10.3389/fimmu.2022.984520
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