The CGRP/macrophage axis signal facilitates inflammation recovery in the intestine

Clin Immunol. 2022 Dec:245:109154. doi: 10.1016/j.clim.2022.109154. Epub 2022 Oct 13.

Abstract

The mechanism of the recovery of immune inflammation in the intestine remains to be investigated. The calcitonin-related protein (CGRP; neuropeptide) has immune regulatory capacity. We observed that lower levels of CGRP were found in the colon biopsies of UC patients. CGRP were negatively correlated to TNF-α, IL-1β and IFN-γ in biopsy samples. The levels of TGF-β were lower in the UC group than that of the normal control (NC) group, which were positively correlated with the CGRP levels. Blocking CGRP significantly delayed recovery from colitis inflammation. CGRP induced the TGF-β-expressing CD4+ Tim4+ macrophages in the intestine. CD4+ Tim4+ macrophages demonstrated immune regulatory function in suppressing proliferation of isolated T cells of colitis and induced apoptosis of T cells. Ablation of the Tgfb1 expression in macrophages resulted in a significant delay in recovery of inflammation in colitis, which was rescued by reconstitution of the CD4+ Tim4+ macrophages in mice.

Keywords: CGRP; Immune response; Inflammation; Intestine; Macrophage; Neuropeptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide* / metabolism
  • Calcitonin Gene-Related Peptide* / pharmacology
  • Colitis*
  • Inflammation
  • Intestines
  • Macrophages
  • Mice
  • Transforming Growth Factor beta

Substances

  • Calcitonin Gene-Related Peptide
  • Transforming Growth Factor beta