Laurence Chapuy1, Marwa Bsat1, Manuel Rubio1, Sisi Sarkizova2,3, Amélie Therrien1,4, Mickael Bouin4, Katarzina Orlicka4, Audrey Weber4, Geneviève Soucy4, Alexandra-Chloé Villani3,5, Marika Sarfati1. 1. Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montréal, QC, Canada. 2. Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. 3. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 4. Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal, Montréal, QC, Canada. 5. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
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.
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 memoryIL-8-producing CD4+ T cells, which might all contribute to the pathogenesis of UC.
Authors: Ji Li; Aito Ueno; Miriam Fort Gasia; Joanne Luider; Tie Wang; Christina Hirota; Humberto B Jijon; Mailin Deane; Michael Tom; Ronald Chan; Herman W Barkema; Paul L Beck; Gilaad G Kaplan; Remo Panaccione; Jiaming Qian; Marietta Iacucci; Xinyang Gui; Subrata Ghosh Journal: Inflamm Bowel Dis Date: 2016-08 Impact factor: 5.325
Authors: Sebastian Zundler; Emily Becker; Marta Spocinska; Monique Slawik; Loreto Parga-Vidal; Regina Stark; Maximilian Wiendl; Raja Atreya; Timo Rath; Moritz Leppkes; Kai Hildner; Rocío López-Posadas; Sören Lukassen; Arif B Ekici; Clemens Neufert; Imke Atreya; Klaas P J M van Gisbergen; Markus F Neurath Journal: Nat Immunol Date: 2019-01-28 Impact factor: 25.606