Front Immunol. 2022 Oct 10:13:984520.doi: 10.3389/fimmu.2022.984520. eCollection 2022.(IF:8.787).

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

Affiliations

Affiliations

  • 1 Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, School of Medicine, Henan University, Kaifeng, China.
  • 2 Institute of Translational Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, China.

Free PMC article

Abstract

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.

Keywords: IL-6; Ocilrp2; Syk; TLR4; inflammation; macrophages.

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