LRCH1 suppresses migration of CD4+ T cells and refers to disease activity in ulcerative colitis

Int J Med Sci. 2020 Feb 17;17(5):599-608. doi: 10.7150/ijms.39106. eCollection 2020.

Abstract

Background: Ulcerative colitis (UC) is a chronically remittent and progressive inflammatory disorder. LRCH1 is reported to be involved in the immune-regulation of several diseases. However, the exact roles of LRCH1 in UC are still obscure. Materials and Methods: LRCH1 expression was analyzed in the inflamed mucosa and peripheral blood mononuclear cells (PBMCs) from patients with UC by quantitative RT-PCR and immunohistochemistry. Peripheral blood CD4+ T cells were transfected with lentivirus-expressing LRCH1 (LV-LRCH1) or LV-sh-LRCH1, and cytokine expression was determined by using flow cytometry, quantitative RT-PCR and ELISA. Transfected CD4+ T cells were harvested to examine the capacity of chemotaxis using Transwell plate. Results: LRCH1 expression was highly decreased in colonic mucosa and PBMCs from patients with A-UC, and negatively correlated with disease activity. Up or down regulation of LRCH1 did not affect the differentiation of CD4+ T cells, and the related cytokines expression. Moreover, LRCH1 inhibited migratory capacity of CD4+ T cells toward CXCL12 by PKCα. Conclusion: LRCH1 plays an important role in the pathogenesis of UC, possibly through modulating the migration of CD4+ T cells. Therefore, targeting LRCH1 might serve as a novel therapeutic approach in the management of UC.

Keywords: CD4+ T cells; LRCH1; migration; ulcerative colitis.

MeSH terms

  • CD4-Positive T-Lymphocytes / physiology*
  • Case-Control Studies
  • Cell Movement
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism*
  • Humans
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Microfilament Proteins / metabolism*

Substances

  • LRCH1 protein, human
  • Microfilament Proteins