CD14型
川地163
免疫系统
生物
免疫学
炎症性肠病
转录组
人口
炎症
巨噬细胞
单核细胞
细胞
疾病
医学
基因表达
病理
基因
遗传学
体外
环境卫生
作者
Laurence Chapuy,Marwa Bsat,Siranush Sarkizova,Manuel Rubio,Amelie Therrien,Evelyne Wassef,Mickael Bouin,Katarzina Orlicka,Audrey Weber,Nir Hacohen,Alexandra-Chloé Villani,Marika Sarfati
标识
DOI:10.1038/s41385-018-0126-0
摘要
Inflammatory bowel diseases are associated with dysregulated immune responses in the intestinal tissue. Four molecularly identified macrophage subsets control immune homeostasis in healthy gut. However, the specific roles and transcriptomic profiles of the phenotypically heterogeneous CD14+ macrophage-like population in inflamed gut remain to be investigated in Crohn's disease (CD). Here we identified two phenotypically, morphologically and functionally distinct colonic HLADR+SIRPα+CD14+ subpopulations that were further characterized using single-cell RNA-sequencing (scRNAseq) in CD. Frequencies of CD64hiCD163-/dim cells selectively augmented in inflamed colon and correlated with endoscopic score of disease severity. IL-1β and IL-23-producing CD64hiCD163-/dim cells predominated over TNF-α-producing CD64hiCD163hi cells in lesions. Purified "inflammatory monocyte-like" CD163-, but not "macrophage-like" CD163hi cells, through IL-1β, promoted Th17/Th1 but not Th1 responses in tissue memory CD4+T cells. Unsupervised scRNAseq analysis that captures the entire HLADR+SIRPα+ population revealed six clusters, two of which were enriched in either CD163- or CD163hi cells, and best defined by TREM1/FCAR/FCN1/IL1RN or CD209/MERTK/MRCI/CD163L1 genes, respectively. Selected newly identified discriminating markers were used beyond CD163 to isolate cells that shared pro-Th17/Th1 function with CD163- cells. In conclusion, a molecularly distinct pro-inflammatory CD14+ subpopulation accumulates in inflamed colon, drives intestinal inflammatory T-cell responses, and thus, might contribute to CD disease severity.
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