Chapuy Laurence, Bsat Marwa, Rubio Manuel, Harvey François, Motta Vinicius, Schwenter Frank, Wassef Ramses, Richard Carole, Deslandres Colette, Nguyen Bich N, Soucy Geneviève, Hacohen Nir, Fritz Jorge, Villani Alexandra-Chloé, Mehta Heena, Sarfati Marika
Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal [CRCHUM], Montréal, QC, Canada.
Department of Biomedical Informatics, Centre de Recherche du Centre Hospitalier de l'Université de Montréal [CRCHUM], Montréal, QC, Canada.
J Crohns Colitis. 2020 Mar 13;14(3):393-405. doi: 10.1093/ecco-jcc/jjz156.
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.
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.
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.
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.
克罗恩病（CD）和溃疡性结肠炎（UC）是炎症性肠病的不同形式。据报道，肠道组织中存在HLA-DR+SIRPα+单核吞噬细胞（MNP）的异质性，包括巨噬细胞（MΦ）、单核细胞衍生（Mono）细胞和树突状细胞（DC），但尚未在炎症性肠病（IBD）患者的肠系膜淋巴结（MLN）中进行研究。我们在此比较了CD和UC的MLN中HLA-DR+SIRPα+MNP的表型、功能和分子特征。
在UC（n = 14）、CD（n = 35）和非IBD（n = 12）患者的MLN中检测了HLA-DR+SIRPα+MNP的细胞分布、形态、免疫功能以及转录组（批量RNA测序）和高维蛋白质表达谱（细胞质谱流式技术）。
显示单核细胞/MΦ形态和吞噬功能的CD14+CD64+CD163+（Mono/MΦ样）MNP频率升高是UC的MLN的一个显著特征。在CD中，相对于Mono/MΦ样细胞，CD14-CD64-CD163-（DC样）细胞的比例增加；DC样细胞驱动幼稚T细胞增殖、Th1极化和Th17中央记忆细胞可塑性。基因表达谱证实了DC样细胞的性质，以BTLA、SERPINF、IGJ最为典型，而Mono/MΦ样细胞则由CD163、MARCO、MAFB、CD300E、S100A9的表达来定义。细胞质谱流式分析表明，在DC样细胞中，CD123+浆细胞样细胞多于传统DC。在Mono/MΦ样细胞中发现了四个CD163+簇，其中两个富含MARCO-CD68dimHLA-DRdim单核细胞样细胞和MARCOhiCD68hiHLA-DRhi MΦ，其比例在UC中相对于CD增加。
确定MLN中MNP的情况为仅在UC中CD163+Mono/MΦ样细胞的扩增提供了证据，突出了UC和CD之间的区别，从而也表明了单核细胞样细胞在驱动结肠炎中的潜在作用。
