JMJD3 regulates CD4 T cell trafficking by targeting actin cytoskeleton regulatory gene Pdlim4

The Journal of Clinical Investigation
Chuntang FuRong-Fu Wang

Abstract

Histone H3K27 demethylase, JMJD3 plays a critical role in gene expression and T-cell differentiation. However, the role and mechanisms of JMJD3 in T cell trafficking remain poorly understood. Here we show that JMJD3 deficiency in CD4+ T cells resulted in an accumulation of T cells in the thymus, and reduction of T cell number in the secondary lymphoid organs. We identified PDLIM4 as a significantly down-regulated target gene in JMJD3-deficient CD4+ T cells by gene profiling and ChIP-seq analyses. We further showed that PDLIM4 functioned as an adaptor protein to interact with S1P1 and filamentous actin (F-actin), thus serving as a key regulator of T cell trafficking. Mechanistically, JMJD3 bound to the promoter and gene body regions of Pdlim4 gene and regulated its expression by interacting with zinc finger transcription factor KLF2. Our findings have identified Pdlim4 as a JMJD3 target gene that affects T-cell trafficking by cooperating with S1P1, and provided insights into the molecular mechanisms by which JMJD3 regulates genes involved in T cell trafficking.

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Citations

May 30, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Eleanor C SemmesKyle M Walsh
Dec 15, 2020·Developmental Cell·Carolina GuibentifJohn C Marioni
Apr 18, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tianhao XuGustavo J Martinez
Jul 2, 2021·Analytical Cellular Pathology (Amsterdam)·Yu-Gui ZhangXing-Ke Yan

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Datasets Mentioned

BETA
GSE58775

Methods Mentioned

BETA
FACS
flow cytometry
PCR
co-IP
ChIP-Seq
ChIP-PCR
Assay
Immunoprecipitation

Software Mentioned

ELAND
NIS
DEGseq
Ingenuity
Elements Analysis

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