Journal
JOURNAL OF CROHNS & COLITIS
Volume 14, Issue 3, Pages 393-405Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ecco-jcc/jjz156
Keywords
Mesenteric lymph nodes; dendritic cells; monocytes; macrophages; RNAseq; mass cytometry; Crohn's disease; ulcerative colitis
Categories
Funding
- Canadian Institutes of Health Research [MOP] [130533]
- Banting Postdoctoral Fellowship
- Fonds de Recherche en Sante du Quebec
- National Human Genome Research Institute Centers of Excellence in Genomics Science grant [P50 HG006193]
- National Human Genome Research grant [T32 HG002295]
Ask authors/readers for more resources
Background and Aims: Crohn's disease [CD] and ulcerative colitis [UC] are distinct forms of inflammatory bowel disease. Heterogeneity of HLA-DR+SIRP alpha(+) mononuclear phagocytes [MNPs], including macrophages [M Phi], monocyte-derived [Mono] cells, and dendritic cells [DCs], was reported in gut tissue but not yet investigated in mesenteric lymph nodes [MLNs] of IBD patients. We here compared the phenotype, function, and molecular profile of HLA-DR+SIRP alpha(+) MNPs in CD and UC MLNs. Methods: Cell distribution, morphology, immune function, and transcriptomic [bulk RNAseq] and high-dimensional protein expression profiles [CyTOF] of HLA-DR+SIRP alpha(+) MNPs were examined in MLNs of UC [n = 14], CD [n = 35], and non-IBD [n = 12] patients. Results: Elevated frequencies of CD14(+)CD64(+)CD163(+) [Mono/M Phi-like] MNPs displaying monocyte/M Phi morphology and phagocytic function were a distinct feature of UC MLNs. In CD, the proportion of CD14(-)CD64(-)CD163(-). [DC-like] cells was augmented relative to Mono/M Phi-like cells; DC-like cells drove naive T cell proliferation, Th1 polarisation, and Th17 T-CM, plasticity. Gene expression profile corroborated the nature of DC-like cells, best represented by BTLA, SERPINF, IGJ and, of Mono/M Phi-like cells, defined by CD163, MARCO, MAFB, CD300E, S100A9 expression. CyTOF analysis showed that CD123(+) plasmacytoid cells predominated over conventional DCs in DC-like cells. Four CD163(+) clusters were revealed in Mono/M Phi-like cells, two of which were enriched in MARCO CD68(dim)HLA-DRdim monocyte-like cells and MARCO(hi)CD68(hi)HLA-DRhi M phi, whose proportion increased in UC relative to CD. Conclusions: Defining the landscape of MNPs in MLNs provided evidence for expansion of CD163(+) Mono/M Phi-like cells in UC only, highlighting a distinction between UC and CD, and thus the potential contribution of monocyte-like cells in driving colitis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available