Pro-inflammatory NK-like T cells are expanded in the blood and inflamed intestine in Crohn's disease.

IF 7.9 2区 医学 Q1 IMMUNOLOGY
Cristina M Chiarolla, Axel R Schulz, Michael Meir, Sebastian Ferrara, Yin Xiao, Simone Reu-Hofer, Addi J Romero-Olmedo, Valeria Falcone, Katja Hoffmann, Maike Büttner-Herold, Martina Prelog, Andreas Rosenwald, Hartmut Hengel, Michael Lohoff, Hyun-Dong Chang, Nicolas Schlegel, Henrik E Mei, Friederike Berberich-Siebelt
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引用次数: 0

Abstract

Altered intestinal immune homeostasis leads to chronic inflammation in Crohn's disease (CD). To address disease- and tissue-specific alterations, we performed a T cell-centric mass cytometry analysis of peripheral and intestinal lymphocytes from patients with CD and healthy donors' PBMCs. Chronic intestinal inflammation enforced activation, exhaustion, and terminal differentiation of CD4+ and CD8+ T cells and a relative enrichment of CD4+ regulatory T (Treg) cells. Moreover, enigmatic rare Treg subsets appeared upon inflammation, e.g. CD4+FOXP3+HLA-DR+TIGIT- and CD4+FOXP3+CD56+, expressing pro-inflammatory IFN-γ upon in vitro stimulation. Some conventional T (Tcon) cells acquired NK-like features. In CD patients' blood, not well studied CD16+CCR6+CD127+ T cells appeared, being CD4+ or CD8+, a phenotype inducible on healthy T cells by CD blood plasma. Upon CD16-mediated antibody binding, they could attain effector function. These findings suggest an uncommon pro-inflammatory innate-like differentiation of Treg and Tcon cells with acquisition of non-specific cytotoxicity. Most likely, this is both cause and consequence of intestinal inflammation during CD.

在克罗恩病患者的血液和发炎的肠道中,促炎性 NK 样 T 细胞大量繁殖。
肠道免疫平衡的改变导致了克罗恩病(CD)的慢性炎症。针对疾病和组织特异性改变,我们对克罗恩病患者的外周和肠道淋巴细胞以及健康供体的 PBMCs 进行了以 T 细胞为中心的质谱分析。慢性肠道炎症导致 CD4+ 和 CD8+ T 细胞活化、衰竭和终末分化,CD4+ 调节性 T(Treg)细胞相对富集。此外,炎症时还会出现神秘的稀有 Treg 亚群,如 CD4+FOXP3+HLA-DR+TIGIT- 和 CD4+FOXP3+CD56+,体外刺激时可表达促炎性 IFN-γ。一些常规 T(Tcon)细胞具有类似 NK 的特征。在 CD 患者的血液中,出现了研究不多的 CD16+CCR6+CD127+ T 细胞,它们是 CD4+ 或 CD8+,这是 CD 血浆在健康 T 细胞上诱导的表型。在 CD16 介导的抗体结合后,它们可以获得效应功能。这些研究结果表明,Treg 和 Tcon 细胞具有不常见的促炎症先天性样分化,并获得非特异性细胞毒性。这很可能是 CD 期间肠道炎症的原因和结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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