溃疡性结肠炎及克罗恩病的免疫细胞亚群差异
创作:szx 审核:szx 06月16日
  • 与对照相比,IBD患者的结肠粘膜中HLA- DR+ CD38+ T细胞、CXCR3+ 浆母细胞、IL-1B+ 巨噬细胞及单核细胞增加;
  • UC患者结肠粘膜中,IL17A+ CD161+ 效应记忆T细胞、IL-17A+ Treg、HLA- DR+ CD56+ 粒细胞增加,ILC3减少;
  • CD患者结肠粘膜中,IL1B+ HLA- DR+ CD38+ T细胞、IL1B+ TNF+ IFNG+ naive B细胞、IL1B+ DC、IL1B+ 浆细胞样DC增加;
  • 活动性CD患者的PBMC中,IL1B+ Treg、IL1B+ DC、IL1B+ 浆细胞样DC、IL1B+ 单核细胞增加,ILC1减少。
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szx
来自Gastroenterology上发表的一项最新研究,利用质谱流式细胞(CyTOF)技术及单细胞RNA测序技术,分析对比了溃疡性结肠炎(UC)与克罗恩病(CD)患者的结肠粘膜及血液中的免疫细胞,鉴定出了不同患者(包括活动性UC、活动性CD、非活动性UC、非活动性CD)的结肠及血液中富集的免疫细胞亚群。该研究结果提示,未来或可靶向特定免疫细胞亚群以治疗不同类型的IBD。
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Gastroenterology [IF:17.373]

Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease

对结肠及血液的单细胞分析揭示溃疡性结肠炎及克罗恩病的不同免疫细胞特征

10.1053/j.gastro.2020.04.074

05-16, Article

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Background & Aims: Studies are needed to determine the mechanisms of mucosal dysregulation in patients with inflammatory bowel diseases (IBD) and differences in inflammatory responses of patients with ulcerative colitis (UC) vs Crohn’s disease (CD). We used mass cytometry (CyTOF) to characterize and compare immune cell populations in the mucosa and blood from patients with IBD and without IBD (controls) at single-cell resolution.
Methods: We performed CyTOF analysis of colonic mucosa samples (n=87) and peripheral blood mononuclear cells (PBMCs, n=85) from patients with active or inactive UC or CD and controls. We also performed single-cell RNA-sequencing, flow cytometry, and RNA in situ hybridization analyses to validate key findings. We used random forest modeling to identify differences in signatures across subject groups.
Results: Compared with controls, colonic mucosa samples from patients with IBD had increased abundances of HLA-DR+CD38+ T cells, including T-regulatory cells that produce inflammatory cytokines; CXCR3+ plasmablasts; and IL1B+ macrophages and monocytes. Colonic mucosa samples from patients with UC were characterized by expansion of IL17A+ CD161+ effector memory T cells and IL17A+ T-regulatory cells; expansion of HLA-DR+CD56+ granulocytes; and reductions in type 3 innate lymphoid cells. Mucosal samples from patients with active CD were characterized by IL1B+HLA-DR+CD38+ T cells, IL1B+TNF+IFNG+ naïve B cells, IL1B+ dendritic cells (DCs), and IL1B+ plasmacytoid DCs. PBMCs from patients with active CD differed from those of active UC in that the PBMCs from patients with CD had increased IL1B+ T-regulatory cells, IL1B+ DCs and IL1B+ plasmacytoid DCs, IL1B+ monocytes, and fewer group 1 innate lymphoid cells. Random forest modeling differentiated active UC from active CD in colonic mucosa and blood samples; top discriminating features included many of the cellular populations identified above.
Conclusions: We used single-cell technologies to identify immune cell populations specific to mucosa and blood samples from patients with active or inactive CD and UC and controls. This information might be used to develop therapies that target specific cell populations in patients with different types of IBD.

First Authors:
Vanessa Mitsialis

Correspondence Authors:
Scott B Snapper,Liza Konnikova

All Authors:
Vanessa Mitsialis,Sarah Wall,Peng Liu,Jose Ordovas-Montanes,Tamar Parmet,Marko Vukovic,Dennis Spencer,Michael Field,Collin McCourt,Jessica Toothaker,Athos Bousvaros,BCH IBD Center,BWH Crohn s and Colitis Center,Alex K Shalek,Leslie Kean,Bruce Horwitz,Jeffrey Goldsmith,George Tseng,Scott B Snapper,Liza Konnikova

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