Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease.
Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease.
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DOI：
10.3389/fimmu.2022.893803
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
慢性肠道炎症是炎症性肠病（IBD）的基础。先前的研究表明细胞免疫系统发生了变化；然而，同时询问所有免疫细胞亚群的作用一直具有挑战性。因此，我们旨在利用高维细胞计数技术鉴定与IBD炎症相关的免疫细胞类型。我们在两个独立的队列中分析了188份肠道活检和配对血液样本，这些样本来自新诊断、未接受治疗的患者（n=42）和对照组（n=26）。我们应用了大规模细胞术（36抗体面板）来分离单个细胞，并使用无偏的分层- sne分析数据。此外，通过成像-质量细胞术（IMC）揭示组织中免疫亚群的空间分布。我们确定了44个不同的免疫亚群。相关网络分析确定了炎症相关亚群网络，包括HLA-DR+CD38+ EM CD4+ T细胞，T调节样细胞，PD1+ EM CD8+ T细胞，中性粒细胞，CD27+ TCRγδ细胞和NK细胞。在第二个队列中验证了所有疾病相关亚群。该网络在一部分患者中丰富，独立于IBD亚型、严重程度或肠道位置。在血液中检测到假定与疾病相关的CD4+ T细胞。最后，成像-质量细胞术显示了中性粒细胞、记忆CD4+ T细胞和髓样细胞在炎症肠中的空间共定位。我们的研究表明，先天免疫细胞和适应性免疫细胞的细胞网络在一部分患者的炎症活检中共定位。这些结果有助于解剖疾病的异质性，并可能指导IBD靶向治疗的发展。
Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR+CD38+ EM CD4+ T cells, T regulatory-like cells, PD1+ EM CD8+ T cells, neutrophils, CD27+ TCRγδ cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4+ T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4+ T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD.
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外周血 Ia 阳性 T 细胞。某些疾病和免疫后增加。
影响因子：
15.3
作者：
Yu, D T;Winchester, R J;Fu, S M;Gibofsky, A;Ko, H S;Kunkel, H G
通讯作者：
Kunkel, H G
影响因子：
64.5
作者：
Kinchen J;Chen HH;Parikh K;Antanaviciute A;Jagielowicz M;Fawkner-Corbett D;Ashley N;Cubitt L;Mellado-Gomez E;Attar M;Sharma E;Wills Q;Bowden R;Richter FC;Ahern D;Puri KD;Henault J;Gervais F;Koohy H;Simmons A
通讯作者：
Simmons A
影响因子：
29.4
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
通讯作者：
Konnikova L
影响因子：
3.7
作者：
Abdelaal, Tamim;van Unen, Vincent;Mahfouz, Ahmed
通讯作者：
Mahfouz, Ahmed
影响因子：
64.5
作者：
Martin, Jerome C.;Chang, Christie;Kenigsberg, Ephraim
通讯作者：
Kenigsberg, Ephraim