Restoring Treg/Th17 cell balance in ulcerative colitis through HRas silencing and MAPK pathway inhibition

Int Immunopharmacol. 2024 Mar 30:130:111608. doi: 10.1016/j.intimp.2024.111608. Epub 2024 Mar 1.

Abstract

This study investigates HRas-dependent mechanisms in the disruption of regulatory T (Treg) cells and T helper 17 (Th17) cells balance in ulcerative colitis (UC). Comprehensive RNA sequencing and bioinformatics analyses revealed elevated HRas and MAPK pathway-related protein expression in UC samples. Using a murine UC model induced by dextran sulfate sodium (DSS), HRas silencing was found to promote Treg cell differentiation and suppress Th17 cell production, effectively restoring balance. Inactivation of the MAPK pathway played a pivotal role in this rebalancing effect. In vivo experiments further confirmed that HRas silencing mitigated colon tissue damage in DSS-induced mice, emphasizing its potential as a therapeutic strategy for UC.

Keywords: HRas silencing; MAPK pathway; RNA sequencing; Th17 cells; Treg cells; Treg/Th17 imbalance; Ulcerative colitis.

MeSH terms

  • Animals
  • Cell Differentiation
  • Colitis* / drug therapy
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / genetics
  • Colon
  • Dextran Sulfate / pharmacology
  • Disease Models, Animal
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory
  • Th17 Cells

Substances

  • Dextran Sulfate