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.