JMJD3 Promotes Lipopolysaccharide-Induced Th17-Cell Differentiation by Modulating the STAT3-RORc Signaling Pathway

Overview

Journal DNA Cell Biol

Publisher Mary Ann Liebert

Specialties Cell Biology
Molecular Biology

Date 2022 Jul 22

PMID 35867069

Authors

Doudou Huang

Chi Zhang

Panpan Wang

Xiting Li

Li Gao

Chuanjiang Zhao

Affiliations

Soon will be listed here.

Abstract

The immune response mediated by Th17 cells is essential in the pathogenesis of periodontitis. Emerging evidence has demonstrated that lipopolysaccharide from (Pg-LPS) could promote Th17-cell differentiation directly, while the downstream signaling remains elusive. This study was aimed to explore the role of JMJD3 (a JmjC family histone demethylase) and signal transducers and activators of transcription 3 (STAT3) in Th17-cell differentiation triggered by Pg-LPS and clarify the interaction between them. We found that the expression of JMJD3 and STAT3 was significantly increased under Th17-polarizing conditions. Pg-LPS could promote Th17-cell differentiation from CD4 T cells, with an increased expression of JMJD3 and STAT3 compared to the culture without Pg-LPS. The coimmunoprecipitation results showed that the interactions of JMJD3 and STAT3, STAT3 and retinoid-related orphan nuclear receptor γt (RORγt) were enhanced following Pg-LPS stimulation during Th17-cell differentiation. Further blocking assays were performed and the results showed that inhibition of STAT3 or JMJD3 both suppressed the Th17-cell differentiation, JMJD3 inhibitor could reduce the expression of STAT3 and p-STAT3, while JMJD3 expression was not affected when STAT3 was inhibited. Taken together, this study found that JMJD3 could promote Pg-LPS induced Th17-cell differentiation by modulating the STAT3-RORc signaling pathway.

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