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

Daiki Yamada, Yudai Kojima, Akinori Hosoya, Masahiro Suzuki, Taro Watabe, Tadahiko Inoue, Naoya Tsugawa, Takehito Asakawa, Yuki Yonemoto, Michio Onizawa, Yasuhiro Nemoto, Shigeru Oshima, Motoyuki Shimonaka, Keiji Kuba, Junji Ishida, Akiyoshi Fukamizu, Josef M. Penninger, Mamoru Watanabe, Ryuichi Okamoto, Takashi Nagaishi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)72-79
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume647
DOIs
Publication statusPublished - Mar 5 2023

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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