IL-17RD/sef exacerbates experimental mouse colitis and inflammation-associated tumorigenesis by regulating the proportion of T cell subsets

FEBS Lett. 2022 Feb;596(4):427-436. doi: 10.1002/1873-3468.14266. Epub 2022 Jan 21.

Abstract

T helper cells, especially Th1 and Th17 cells, were reported to play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). However, the underlying factors regulating T cell functions in IBD progression remain to be fully elucidated. Here, we revealed that IL-17RD/Sef exacerbates DSS-induced colitis by regulating the balance of T cell subsets and their secretion of associated cytokines. We also observed that IL-17RD/Sef promotes colitis-associated tumorigenesis and negatively correlates with survival in both mouse and colorectal cancer patients. Our results suggested that IL-17RD/Sef functions as a regulator of T cell subsets to promote the inflammatory responses in the pathogenesis of IBD and colitis-associated colon cancer.

Keywords: IL-17RD/Sef; T cell subsets; colitis-associated colon cancer; inflammatory bowel diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / immunology*
  • Carcinogenesis / pathology
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / immunology*
  • Colitis / mortality
  • Colon / immunology
  • Colon / pathology
  • Dextran Sulfate / administration & dosage
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Inflammation
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Lymphocyte Count
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction
  • Survival Analysis
  • Th1 Cells / immunology*
  • Th1 Cells / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • IFNG protein, mouse
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • Membrane Proteins
  • Sef protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Interleukin-4
  • Interferon-gamma
  • Dextran Sulfate