SWI/SNF chromatin remodeling factor BAF60b restrains inflammatory diseases by affecting regulatory T cell migration

Cell Rep. 2024 Jul 23;43(7):114458. doi: 10.1016/j.celrep.2024.114458. Epub 2024 Jul 10.

Abstract

Regulatory T (Treg) cells play a critical regulatory role in the immune system by suppressing excessive immune responses and maintaining immune balance. The effective migration of Treg cells is crucial for controlling the development and progression of inflammatory diseases. However, the mechanisms responsible for directing Treg cells into the inflammatory tissue remain incompletely elucidated. In this study, we identified BAF60b, a subunit of switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complexes, as a positive regulator of Treg cell migration that inhibits the progression of inflammation in experimental autoimmune encephalomyelitis (EAE) and colitis animal models. Mechanistically, transcriptome and genome-wide chromatin-landscaped analyses demonstrated that BAF60b interacts with the transcription factor RUNX1 to promote the expression of CCR9 on Treg cells, which in turn affects their ability to migrate to inflammatory tissues. Our work provides insights into the essential role of BAF60b in regulating Treg cell migration and its impact on inflammatory diseases.

Keywords: BAF60b; CP: Immunology; CP: Molecular biology; SWI/SNF; inflammation; migration; regulatory T cells.

MeSH terms

  • Animals
  • Cell Movement*
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / metabolism
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / pathology
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Humans
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Mice
  • Mice, Inbred C57BL*
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / metabolism
  • Transcription Factors / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • Transcription Factors
  • Core Binding Factor Alpha 2 Subunit