Tissue-resident memory T cells in epicardial adipose tissue comprise transcriptionally distinct subsets that are modulated in atrial fibrillation

被引：7

作者：

Vyas, Vishal ^{[1
,2
]}

Sandhar, Balraj ^{[1
]}

Keane, Jack M. ^{[1
]}

Wood, Elizabeth G. ^{[1
]}

Blythe, Hazel ^{[1
]}

Jones, Aled ^{[1
]}

Shahaj, Eriomina ^{[1
]}

Fanti, Silvia ^{[1
]}

Williams, Jack ^{[1
]}

Metic, Nasrine ^{[3
]}

Efremova, Mirjana ^{[3
]}

Ng, Han Leng ^{[4
]}

Nageswaran, Gayathri ^{[5
]}

Byrne, Suzanne ^{[5
]}

Feldhahn, Niklas ^{[4
]}

Marelli-Berg, Federica ^{[1
]}

Chain, Benny ^{[5
]}

Tinker, Andrew ^{[1
]}

Finlay, Malcolm C. ^{[1
,2
]}

Longhi, M. Paula ^{[1
]}

机构：

[1] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

[2] St Bartholomews Hosp, Barts Heart Ctr, Dept Cardiol, London, England

[3] Queen Mary Univ London, Canc Res UK, Barts Ctr, London, England

[4] Imperial Coll London, Fac Med, Ctr Haematol, Dept Immunol & Inflammat, London, England

[5] UCL, UCL Div Infect & Immun, London, England

来源：

NATURE CARDIOVASCULAR RESEARCH | 2024年 / 3卷 / 09期

基金：

英国医学研究理事会;

关键词：

HEART-FAILURE; INFLAMMATION; MYOCARDIUM; EXPRESSION; FIBROSIS;

D O I：

10.1038/s44161-024-00532-x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Atrial fibrillation (AF) is the most common sustained arrhythmia and carries an increased risk of stroke and heart failure. Here we investigated how the immune infiltrate of human epicardial adipose tissue (EAT), which directly overlies the myocardium, contributes to AF. Flow cytometry analysis revealed an enrichment of tissue-resident memory T (TRM) cells in patients with AF. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell T cell receptor (TCR) sequencing identified two transcriptionally distinct CD8+ TRM cells that are modulated in AF. Spatial transcriptomic analysis of EAT and atrial tissue identified the border region between the tissues to be a region of intense inflammatory and fibrotic activity, and the addition of TRM populations to atrial cardiomyocytes demonstrated their ability to differentially alter calcium flux as well as activate inflammatory and apoptotic signaling pathways. This study identified EAT as a reservoir of TRM cells that can directly modulate vulnerability to cardiac arrhythmia. Vyas et al. show that epicardial adipose tissue is a reservoir for a subpopulation of tissue-resident memory T cells that can increase the vulnerability of the heart to atrial fibrillation.

引用

页码：1067 / 1082

页数：27

共 67 条

[1] Frequency of elevation of C-reactive protein in atrial fibrillation [J].

Anderson, JL ;

Maycock, CAA ;

Lappé, DL ;

Crandall, BG ;

Horne, BD ;

Bair, TL ;

Morris, SR ;

Li, QY ;

Muhlestein, JB .

AMERICAN JOURNAL OF CARDIOLOGY, 2004, 94 (10) :1255-1259

[2] An interferon gamma response signature links myocardial aging and immunosenescence [J].

Ashour, DiyaaElDin ;

Rebs, Sabine ;

Arampatzi, Panagiota ;

Saliba, Antoine-Emmanuel ;

Dudek, Jan ;

Schulz, Richard ;

Hofmann, Ulrich ;

Frantz, Stefan ;

Cochain, Clement ;

Streckfuss-Boemeke, Katrin ;

Ramos, Gustavo Campos .

CARDIOVASCULAR RESEARCH, 2023, 119 (14) :2458-2468

[3] The fellowship of regulatory and tissue-resident memory cells [J].

Barros, Leandro ;

Ferreira, Cristina ;

Veldhoen, Marc .

MUCOSAL IMMUNOLOGY, 2022, 15 (01) :64-73

[4] Inflammation-induced formation of fat-associated lymphoid clusters [J].

Benezech, Cecile ;

Luu, Nguyet-Thin ;

Walker, Jennifer A. ;

Kruglov, Andrei A. ;

Loo, Yunhua ;

Nakamura, Kyoko ;

Zhang, Yang ;

Nayar, Saba ;

Jones, Lucy H. ;

Flores-Langarica, Adriana ;

McIntosh, Alistair ;

Marshall, Jennifer ;

Barone, Francesca ;

Besra, Gurdyal ;

Miles, Katherine ;

Allen, Judith E. ;

Gray, Mohini ;

Kollias, George ;

Cunningham, Adam F. ;

Withers, David R. ;

Toellner, Kai Michael ;

Jones, Nick D. ;

Veldhoen, Marc ;

Nedospasov, Sergei A. ;

McKenzie, Andrew N. J. ;

Caamano, Jorge H. .

NATURE IMMUNOLOGY, 2015, 16 (08) :819-+

[5] KLRG1 and CD103 Expressions Define Distinct Intestinal Tissue-Resident Memory CD8 T Cell Subsets Modulated in Crohn's Disease [J].

Bottois, Hugo ;

Ngollo, Marjolaine ;

Hammoudi, Nassim ;

Courau, Tristan ;

Bonnereau, Julie ;

Chardiny, Victor ;

Grand, Celine ;

Gergaud, Brice ;

Allez, Matthieu ;

Le Bourhis, Lionel .

FRONTIERS IN IMMUNOLOGY, 2020, 11

[6] Atrial fibrillation in the UK: predicting costs of an emerging epidemic recognizing and forecasting the cost drivers of atrial fibrillation-related costs [J].

Burdett, Paul ;

Lip, Gregory Y. H. .

EUROPEAN HEART JOURNAL-QUALITY OF CARE AND CLINICAL OUTCOMES, 2022, 8 (02) :187-194

[7] Arthritis flares mediated by tissue-resident memory T cells in the joint [J].

Chang, Margaret H. ;

Levescot, Anais ;

Nelson-Maney, Nathan ;

Blaustein, Rachel B. ;

Winden, Kellen D. ;

Morris, Allyn ;

Wactor, Alexandra ;

Balu, Spoorthi ;

Grieshaber-Bouyer, Ricardo ;

Wei, Kevin ;

Henderson, Lauren A. ;

Iwakura, Yoichiro ;

Clark, Rachael A. ;

Rao, Deepak A. ;

Fuhlbrigge, Robert C. ;

Nigrovic, Peter A. .

CELL REPORTS, 2021, 37 (04)

[8] Increased inflammatory cell infiltration in the atrial myocardium of patients with atrial fibrillation [J].

Chen, Mien-Cheng ;

Chang, Jen-Ping ;

Liu, Wen-Hao ;

Yang, Cheng-Hsu ;

Chen, Yung-Lung ;

Tsai, Tzu-Hsien ;

Wang, Ya-Hui ;

Pan, Kuo-Li .

AMERICAN JOURNAL OF CARDIOLOGY, 2008, 102 (07) :861-865

[9] Structural remodeling in atrial fibrillation [J].

Corradi, Domenico ;

Callegari, Sergio ;

Maestri, Roberta ;

Benussi, Stefano ;

Alfieri, Ottavio .

NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE, 2008, 5 (12) :782-796

[10] Deep phenotyping of human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes [J].

Cyganek, Lukas ;

Tiburcy, Malte ;

Sekeres, Karolina ;

Gerstenberg, Kathleen ;

Bohnenberger, Hanibal ;

Lenz, Christof ;

Henze, Sarah ;

Stauske, Michael ;

Salinas, Gabriela ;

Zimmermann, Wolfram-Hubertus ;

Hasenfuss, Gerd ;

Guan, Kaomei .

JCI INSIGHT, 2018, 3 (12)

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