Apelin expression is downregulated in T cells in a murine model of chronic colitis

Biochem Biophys Res Commun. 2023 Mar 5:647:72-79. doi: 10.1016/j.bbrc.2023.01.068. Epub 2023 Jan 21.

Abstract

Apelin (APL), an endogenous ligand for APJ, has been reported to be upregulated in a murine model of acute colitis induced by sodium dextran sulfate, as well as inflammatory bowel diseases (IBD) in humans. However, the mechanisms and functions of APL/APJ axis in the pathogenesis of IBD are unclear. We herein analyzed CD4+ T cells to determine the functions of APL in a murine model of chronic colitis induced in Rag deficient mice (Rag-/-). In colonic tissues of wild-type mice (WT), we found that APL was expressed especially in the lamina propria lymphocytes, where CD4+ T cells are dominant, rather than the epithelial cells. Unexpectedly, the APL expression was rather downregulated in the colonic tissue of the chronic colitis group compared to the control groups (Rag-/- before colitis induction and WT). The APL expression was downregulated when naïve T cells were differentiated into effecter T cells. A lack of APL resulted in decreased naïve T cells and increased effecter T cells in secondary lymphoid organs. A synthetic APL peptide, [Pyr1]-APL-13, increased IL-10 and decreased IFN-γ productions by effecter T cells. Administration of [Pyr1]-APL-13 improved survival rate in association with lessened colitis severity and decreased pro-inflammatory cytokine production. This is the first report showing immunological function of APL specifically on T cells, and these results indicate that APL/APJ axis may be a novel therapeutic target for IBD.

Keywords: APJ; Apelin; Colitis; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apelin / metabolism
  • CD4-Positive T-Lymphocytes
  • Colitis* / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Humans
  • Inflammatory Bowel Diseases* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / metabolism

Substances

  • Apelin
  • Dextran Sulfate