Category: Inflammatory bowel diseases
Background and Aims. CD14+ mononuclear phagocytes (MNPs), neutrophils and T cells infiltrate colon in ulcerative colitis (UC). We here investigated how CD14+MNPs and cytokine they produce, shape colonic effector T cell profile.
Methods. Colonic or mesenteric lymph node (mLNs) CD4+T cells isolated from UC or Crohn’s disease (CD) were stimulated with cytokines or autologous CD14+ MNPs. Cytokine expression was assessed by intracytoplasmic staining and multiplex ELISA. Unsupervised phenotypic multicolor analysis of colonic CD14+ MNPs was performed using 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 the neutrophil-attracting chemokine IL-8 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, mucosal IL-8+ T cells co-expressed GM-CSF, TNF-a and IL-6 ex vivo, which was promoted by IL-12 in the mucosa and mLNs.
Conclusions. Our findings established a link between monocyte-like CD163-MNPs, IL-12, IL-1β and the detection of colonic memory IL-8-producingCD4+T cells, which might all contribute to UC pathogenesis.
Laurence Chapuy– CRCHUM University of Montreal
Marwa Bsat– CRCHUM University of Montreal
Amélie Therrien– CRCHUM University of Montreal
Manuel Rubio– CRCHUM University of Montreal
Audrey Weber– CHUM
Mickael Bouin– CHUM
Geneviève Soucy– CHUM
Sisi Sarkizova– Harvard Medical School,
Alexandra-Chloe Villani– Broad Institute of MIT and Harvard, Center for Immunology and Inflammatory Diseases Massachusetts General Hospital
Marika Sarfati– CRCHUM University of Montreal