IL-12 and Mucosal CD14+ Monocyte-Like Cells Induce IL-8 in Colonic Memory CD4+ T Cells of Patients With Ulcerative Colitis but not Crohn's Disease

J Crohns Colitis. 2020 Jan 1;14(1):79-95. doi: 10.1093/ecco-jcc/jjz115.

Abstract

Background and aims: CD14+ mononuclear phagocytes [MNPs] and T cells infiltrate colon in ulcerative colitis [UC]. Here we investigated how CD14+ MNPs and the cytokines they produce shape the colonic effector T cell profile.

Methods: Colonic or mesenteric lymph node [mLNs] CD4+ T cells isolated from UC or Crohn's disease [CD] patients were stimulated with cytokines or autologous CD14+ MNPs. Cytokine expression was assessed by intracytoplasmic staining and multiplex ELISA. Unsupervised phenotypic multicolour analysis of colonic CD14+ MNPs was performed using the FlowSOM algorithm.

Results: Among CD14+CD64+HLA-DR+SIRPα + MNPs, only the pro-inflammatory cytokine-producing CD163- subpopulation accumulated in inflamed UC colon and promoted mucosal IL-1β-dependent Th17, Th17/Th1, Th17/Th22 but not Th1 responses. Unsupervised phenotypic analysis of CD14+CD64+ MNPs segregated CD163- monocyte-like cells and CD163+ macrophages. Unexpectedly, IL-12, IL-1β and CD163-, but not CD163+, cells induced IL-8 expression in colonic CD4+ T cells, which co-expressed IFN-γ and/or IL-17 in UC and not CD. The CD163- monocyte-like cells increased the frequency of IL-8+IL-17+/-IFN-γ +/- T cells through IL-1β and IL-12. Finally, colonic IL-8+ T cells co-expressing GM-CSF, TNF-α and IL-6 were detected ex vivo and, promoted by IL-12 in the mucosa and mLNs in UC only.

Conclusions: Our findings established a link between monocyte-like CD163- MNPs, IL-12, IL-1β and the detection of colonic memory IL-8-producing CD4+ T cells, which might all contribute to the pathogenesis of UC.

Keywords: Crohn’s disease; IL8; Ulcerative colitis; colonic T cells; colonic mononuclear phagocytes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / physiology*
  • Case-Control Studies
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / pathology
  • Crohn Disease / metabolism*
  • Crohn Disease / pathology
  • Female
  • Humans
  • Interleukin-12 / metabolism*
  • Interleukin-8 / metabolism*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lipopolysaccharide Receptors / metabolism*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Interleukin-8
  • Lipopolysaccharide Receptors
  • Interleukin-12