Category: Inflammatory bowel diseases
Aim: Apelin (APL) has been reported to be upregulated in the colon during acute colitis induced by dextran sodium sulfate (DSS), but the mechanism and function remain unclear. Here, we analyzed APL expression in another colitis model but with chronic inflammation.
Results: Colonic epithelia and lamina propria lymphocytes were isolated from wild type C57BL6 mice (WT) to assess APL expression. Semi-quantitative PCR (qPCR) revealed higher CD4+ T cell expression of APL compared to other cell types including colonic epithelium. Next, naïve T cells isolated from WT were adoptively transferred into Rag deficient mice (Rag-/-) to induce chronic colitis. Interestingly, qPCR showed downregulation of APL in the colon of the Rag-/- induced colitis compared to those without colitis, which is different from previous report with DSS colitis. Therefore, colonic and splenic CD4+ T cells were isolated from WT and T cell-reconstituted Rag-/-. Subsequently, qPCR showed decreased APL expression in T cells from Rag-/- induced colitis compared to that of WT. WT naïve T cells were differentiated into either Th1, Th2 or Th17 in vitro. APL expressions in these differentiated T cells were significantly downregulated compared to that of non-differentiated control. Given these results, Rag-/- receiving naïve T cells were administered synthetic APL peptide to rescue the APL downregulation. This resulted in reduced severity of colitis compared to that of control.
Conclusion: APL downregulation in the effecter T cells may result in the development of chronic colitis, and APL may be a therapeutic target for inflammatory bowel diseases.
Takashi Nagaishi– Associate Professor of Medicine, Tokyo Medical and Dental University
Yudai Kojima– Tokyo Medical and Dental University
Daiki Yamada– Tokyo Medical and Dental University
Taro Watabe– Assistant Professor, Tokyo Medical and Dental University
Naoya Tsugawa– Tokyo Medical and Dental University
Nisha Jose– Tokyo Medical and Dental University
Akinori Hosoya– Tokyo Medical and Dental University
Masahiro Suzuki– Tokyo Medical and Dental University
Michio Onizawa– Tokyo Medical and Dental University
Mamoru Watanabe– Tokyo Medical and Dental University