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

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+SIRP alpha(+) MNPs, only the pro-inflammatory cytokine-producing CD163-subpopulation accumulated in inflamed UC colon and promoted mucosal IL-1 beta-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-1 beta and CD163(-), but not CD163(+), cells induced IL-8 expression in colonic CD4(+)T cells, which co-expressed IFN-gamma and/or IL-17 in UC and not CD. The CD163(-) monocyte-like cells increased the frequency of IL-8(+)IL-17(+/-)IFN-gamma T+/- cells through IL-1 beta and IL-12. Finally, colonic IL-8(+) T cells co-expressing GM-CSF, TNF-alpha 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-1 beta and the detection of colonic memory IL-8-producing CD4(+) T cells, which might all contribute to the pathogenesis of UC.