GSE138364
Transcriptomic analysis and high dimensional phenotypic mapping of mononuclear phagocytes in mesenteric lymph nodes reveal differences between ulcerative colitis and Crohn's disease
Background and Aims: Crohn's disease [CD] and ulcerative colitis [UC] are distinct forms of  inflammatory bowel disease. Heterogeneity of HLA-DR+SIRPa + mononuclear phagocytes [MNPs],  including macrophages [MF], 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+SIRPa+ 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+SIRPa+ 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/MF-like] MNPs displaying monocyte/  MF 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/MF-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/MF-  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/MF-like cells, two of which were enriched in MARCO-CD68dimHLA-DRdim  monocyte-like cells and MARCOhiCD68hiHLA-DRhi M?, whose proportion increased in UC relative to CD.  Conclusions: Defining the landscape of MNPs in MLNs provided evidence for expansion of  CD163+ Mono/MF-like cells in UC only, highlighting a distinction between UC and CD, and thus the  potential contribution of monocyte-like cells in driving colitis. Overall design: Bulk RNA sequencing of FACS-sorted CD14+CD64+CD163+ and CD14-CD64-CD163- populations from MLNs of 5 UC and 7 CD patients