Transcriptomic Analysis and High-dimensional Phenotypic Mapping of Mononuclear Phagocytes in Mesenteric Lymph Nodes Reveal Differences Between Ulcerative Colitis and Crohn's Disease

J Crohns Colitis. 2020 Mar 13;14(3):393-405. doi: 10.1093/ecco-jcc/jjz156.

Abstract

Background and aims: Crohn's disease [CD] and ulcerative colitis [UC] are distinct forms of inflammatory bowel disease. Heterogeneity of HLA-DR+SIRPα + mononuclear phagocytes [MNPs], including macrophages [MΦ], 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+SIRPα + 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+SIRPα + 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/MΦ-like] MNPs displaying monocyte/MΦ 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/MΦ-like cells; DC-like cells drove naïve T cell proliferation, Th1 polarisation, and Th17 TCM plasticity. Gene expression profile corroborated the nature of DC-like cells, best represented by BTLA, SERPINF, IGJ and, of Mono/MΦ-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/MΦ-like cells, two of which were enriched in MARCO-CD68dimHLA-DRdim monocyte-like cells and MARCOhiCD68hiHLA-DRhi Mɸ, whose proportion increased in UC relative to CD.

Conclusions: Defining the landscape of MNPs in MLNs provided evidence for expansion of CD163+ Mono/MΦ-like cells in UC only, highlighting a distinction between UC and CD, and thus the potential contribution of monocyte-like cells in driving colitis.

Keywords: Crohn’s disease; Mesenteric lymph nodes; RNAseq; dendritic cells; macrophages; mass cytometry; monocytes; ulcerative colitis.

MeSH terms

  • Antigens, CD / genetics*
  • Antigens, Differentiation, Myelomonocytic / genetics*
  • Colitis, Ulcerative* / genetics
  • Colitis, Ulcerative* / immunology
  • Colitis, Ulcerative* / pathology
  • Crohn Disease* / genetics
  • Crohn Disease* / immunology
  • Crohn Disease* / pathology
  • Dendritic Cells / immunology
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Lymph Nodes* / immunology
  • Lymph Nodes* / pathology
  • Male
  • Mesentery
  • Middle Aged
  • Mononuclear Phagocyte System* / metabolism
  • Mononuclear Phagocyte System* / pathology
  • Receptors, Cell Surface / genetics*
  • Receptors, IgG / genetics*
  • Receptors, Scavenger / immunology
  • Th17 Cells / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface
  • Receptors, IgG
  • Receptors, Scavenger