Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn's Disease.
Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn's Disease.
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DOI：
10.1053/j.gastro.2020.04.074
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发表时间：
2020-08
期刊：
影响因子：
29.4
通讯作者：
Konnikova L
中科院分区：
文献类型：
--
作者：
Mitsialis V;Wall S;Liu P;Ordovas-Montanes J;Parmet T;Vukovic M;Spencer D;Field M;McCourt C;Toothaker J;Bousvaros A;Boston Children’s Hospital Inflammatory Bowel Disease Center;Brigham and Women’s Hospital Crohn’s and Colitis Center;Shalek AK;Kean L;Horwitz B;Goldsmith J;Tseng G;Snapper SB;Konnikova L
需要进行研究以确定炎症性肠病（IBD）患者的粘膜失调机制以及溃疡性结肠炎（UC）与克罗恩病（CD）患者炎症反应的差异。我们使用质谱细胞术（CyTOF）以单细胞分辨率表征和比较IBD患者和非IBD患者（对照组）粘膜和血液中的免疫细胞群。我们对来自活动性或非活动性UC或CD患者和对照组的结肠粘膜样本（n=87）和外周血单核细胞（PBMC，n=85）进行了CyTOF分析。我们还进行了单细胞RNA测序、流式细胞术和RNA原位杂交分析，以验证关键发现。我们使用随机森林模型来识别不同受试者组之间的签名差异。与对照组相比，IBD患者的结肠粘膜样本中HLA-DR+ CD 38 + T细胞的丰度增加，包括产生炎性细胞因子的T调节细胞; CXCR 3+浆母细胞;和IL 1B+巨噬细胞和单核细胞。来自UC患者的结肠粘膜样品的特征在于IL 17 A + CD 161+效应记忆T细胞和IL 17 A + T调节细胞的扩增; HLA-DR+ CD 56+粒细胞的扩增;和3型先天淋巴样细胞的减少。来自活动性CD患者的粘液样品的特征在于IL 1 B +HLA-DR+ CD 38 + T细胞、IL 1 B +TNF+IFNG+幼稚B细胞、IL 1 B+树突状细胞（DC）和IL 1 B+浆细胞样DC。活动性CD患者的PBMC与活动性UC患者的PBMC不同之处在于，CD患者的PBMC具有增加的IL 1B + T调节细胞、IL 1B + DC和IL 1B+浆细胞样DC、IL 1B+单核细胞和较少的第1组先天性淋巴细胞。随机森林建模区分结肠粘膜和血液样品中的活动性UC与活动性CD;最佳区分特征包括上文鉴定的许多细胞群体。我们使用单细胞技术来鉴定对活动性或非活动性CD和UC患者以及对照组的粘膜和血液样本特异的免疫细胞群。这些信息可能用于开发针对不同类型IBD患者特定细胞群的疗法。作者分析了IBD患者结肠组织和血液样本中的免疫细胞，发现CD与UC患者的样本含有不同类型的免疫细胞。
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. 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. 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. 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. The authors analyzed immune cells in colon tissues and blood samples from patients with IBD and found that samples from patients with CD vs UC contain different types of immune cells.
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DOI：
10.1073/pnas.1905054116
发表时间：
2019-09-17
影响因子：
11.1
作者：
Lok, Laurence S. C.;Dennison, Thomas W.;Clatworthy, Menna R.
通讯作者：
Clatworthy, Menna R.
影响因子：
4.3
作者：
Chen H;Lau MC;Wong MT;Newell EW;Poidinger M;Chen J
通讯作者：
Chen J
影响因子：
32.4
作者：
Bernink, Jochem H.;Krabbendam, Lisette;Spits, Hergen
通讯作者：
Spits, Hergen
影响因子：
3.1
作者：
Mao, Hui;Pan, Fei;Dai, Guanghai
通讯作者：
Dai, Guanghai
影响因子：
4.4
作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
通讯作者：
Haller, David A.