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  • 제21권2호
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  • Pages.17.1-17.10
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  • 2021
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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Increase of Vδ2+ T Cells That Robustly Produce IL-17A in Advanced Abdominal Aortic Aneurysm Tissues

  • In-Ho Seo (Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Seung-Jun Lee (Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine) ;
  • Tae Wook Noh (Department of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine) ;
  • Jung-Hwan Kim (Department of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine) ;
  • Hyun-Chel Joo (Department of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine) ;
  • Eui-Cheol Shin (Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Su-Hyung Park (Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Young-Guk Ko (Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine)
  • 투고 : 2020.11.26
  • 심사 : 2020.12.19
  • 발행 : 2021.04.30
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초록

Abdominal aortic aneurysm (AAA) is a chronic dilation of the aorta with a tendency to enlarge and eventually rupture, which constitutes a major cause of cardiovascular mortality. Although T-cell infiltrates have been observed in AAA, the cellular, phenotypic, and functional characteristics of these tissue-infiltrating T cells are not fully understood. Here, we investigated the proportional changes of T-cell subsets-including CD4+ T cells, CD8+ T cells, and γδ T cells-and their effector functions in AAAs. We found that Vδ2+ T cells were presented at a higher frequency in aortic aneurysmal tissue compared to normal aortic tissue and PBMCs from patients with AAA. In contrast, no differences were observed in the frequencies of CD4+, CD8+, and Vδ1+ T cells. Moreover, we observed that the Vδ2+ T cells from AAA tissue displayed immunophenotypes indicative of CCR5+ non-exhausted effector memory cells, with a decreased proportion of CD16+ cells. Finally, we found that these Vδ2+ T cells were the main source of IL-17A in abdominal aortic aneurysmal tissue. In conclusion, our results suggest that increased Vδ2+ T cells that robustly produce IL-17A in aortic aneurysmal tissue may contribute to AAA pathogenesis and progression.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2020R1C1C1006210 to S.J.L. and NRF-2019R1A2C2005176 to S.H.P.), and also by the Severance Hospital Research fund for Clinical excellence (SHRC) (C-2020-0038 to Y.G.K.).

참고문헌

  1. Golledge J, Muller J, Daugherty A, Norman P. Abdominal aortic aneurysm: pathogenesis and implications for management. Arterioscler Thromb Vasc Biol 2006;26:2605-2613. https://doi.org/10.1161/01.ATV.0000245819.32762.cb
  2. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, Ford E, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:480-486. https://doi.org/10.1161/CIRCULATIONAHA.108.191259
  3. Kent KC. Clinical practice. Abdominal aortic aneurysms. N Engl J Med 2014;371:2101-2108. https://doi.org/10.1056/NEJMcp1401430
  4. Lindeman JH, Matsumura JS. Pharmacologic management of aneurysms. Circ Res 2019;124:631-646. https://doi.org/10.1161/CIRCRESAHA.118.312439
  5. Nordon IM, Hinchliffe RJ, Loftus IM, Thompson MM. Pathophysiology and epidemiology of abdominal aortic aneurysms. Nat Rev Cardiol 2011;8:92-102. https://doi.org/10.1038/nrcardio.2010.180
  6. Quintana RA, Taylor WR. Cellular mechanisms of aortic aneurysm formation. Circ Res 2019;124:607-618. https://doi.org/10.1161/CIRCRESAHA.118.313187
  7. Saigusa R, Winkels H, Ley K. T cell subsets and functions in atherosclerosis. Nat Rev Cardiol 2020;17:387-401. https://doi.org/10.1038/s41569-020-0352-5
  8. Wang SK, Murphy MP. Immune modulation as a treatment for abdominal aortic aneurysms. Circ Res 2018;122:925-927. https://doi.org/10.1161/CIRCRESAHA.118.312870
  9. Chen Q, Wen K, Lv A, Liu M, Ni K, Xiang Z, Liu Y, Tu W. Human Vγ9Vδ2-T cells synergize CD4+ T follicular helper cells to produce influenza virus-specific antibody. Front Immunol 2018;9:599.
  10. Riano F, Karunakaran MM, Starick L, Li J, Scholz CJ, Kunzmann V, Olive D, Amslinger S, Herrmann T. Vγ9Vδ2 TCR-activation by phosphorylated antigens requires butyrophilin 3 A1 (BTN3A1) and additional genes on human chromosome 6. Eur J Immunol 2014;44:2571-2576. https://doi.org/10.1002/eji.201444712
  11. Platsoucas CD, Lu S, Nwaneshiudu I, Solomides C, Agelan A, Ntaoula N, Purev E, Li LP, Kratsios P, Mylonas E, et al. Abdominal aortic aneurysm is a specific antigen-driven T cell disease. Ann N Y Acad Sci 2006;1085:224-235. https://doi.org/10.1196/annals.1383.019
  12. Glatzel A, Wesch D, Schiemann F, Brandt E, Janssen O, Kabelitz D. Patterns of chemokine receptor expression on peripheral blood γδ T lymphocytes: strong expression of CCR5 is a selective feature of Vδ2/Vγ9 γδ T cells. J Immunol 2002;168:4920-4929. https://doi.org/10.4049/jimmunol.168.10.4920
  13. Caccamo N, Battistini L, Bonneville M, Poccia F, Fournie JJ, Meraviglia S, Borsellino G, Kroczek RA, La Mendola C, Scotet E, et al. CXCR5 identifies a subset of Vgamma9Vdelta2 T cells which secrete IL-4 and IL-10 and help B cells for antibody production. J Immunol 2006;177:5290-5295. https://doi.org/10.4049/jimmunol.177.8.5290
  14. Lawand M, Dechanet-Merville J, Dieu-Nosjean MC. Key features of gamma-delta T-cell subsets in human diseases and their immunotherapeutic implications. Front Immunol 2017;8:761.
  15. Morita CT, Verma S, Aparicio P, Martinez C, Spits H, Brenner MB. Functionally distinct subsets of human gamma/delta T cells. Eur J Immunol 1991;21:2999-3007. https://doi.org/10.1002/eji.1830211215
  16. Fenoglio D, Poggi A, Catellani S, Battaglia F, Ferrera A, Setti M, Murdaca G, Zocchi MR. Vdelta1 T lymphocytes producing IFN-gamma and IL-17 are expanded in HIV-1-infected patients and respond to Candida albicans. Blood 2009;113:6611-6618. https://doi.org/10.1182/blood-2009-01-198028
  17. Caccamo N, La Mendola C, Orlando V, Meraviglia S, Todaro M, Stassi G, Sireci G, Fournie JJ, Dieli F. Differentiation, phenotype, and function of interleukin-17-producing human Vγ9Vδ2 T cells. Blood 2011;118:129-138. https://doi.org/10.1182/blood-2011-01-331298
  18. Ness-Schwickerath KJ, Jin C, Morita CT. Cytokine requirements for the differentiation and expansion of IL-17A- and IL-22-producing human Vγ2Vδ2 T cells. J Immunol 2010;184:7268-7280. https://doi.org/10.4049/jimmunol.1000600
  19. Spencer CT, Abate G, Sakala IG, Xia M, Truscott SM, Eickhoff CS, Linn R, Blazevic A, Metkar SS, Peng G, et al. Granzyme A produced by γ9δ2 T cells induces human macrophages to inhibit growth of an intracellular pathogen. PLoS Pathog 2013;9:e1003119.
  20. Qin G, Mao H, Zheng J, Sia SF, Liu Y, Chan PL, Lam KT, Peiris JS, Lau YL, Tu W. Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses. J Infect Dis 2009;200:858-865. https://doi.org/10.1086/605413
  21. Vermijlen D, Ellis P, Langford C, Klein A, Engel R, Willimann K, Jomaa H, Hayday AC, Eberl M. Distinct cytokine-driven responses of activated blood γδ T cells: insights into unconventional T cell pleiotropy. J Immunol 2007;178:4304-4314. https://doi.org/10.4049/jimmunol.178.7.4304
  22. Harly C, Guillaume Y, Nedellec S, Peigne CM, Monkkonen H, Monkkonen J, Li J, Kuball J, Adams EJ, Netzer S, et al. Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset. Blood 2012;120:2269-2279. https://doi.org/10.1182/blood-2012-05-430470
  23. Caccamo N, Todaro M, Sireci G, Meraviglia S, Stassi G, Dieli F. Mechanisms underlying lineage commitment and plasticity of human γδ T cells. Cell Mol Immunol 2013;10:30-34. https://doi.org/10.1038/cmi.2012.42
  24. Cheng HY, Wu R, Gebre AK, Hanna RN, Smith DJ, Parks JS, Ley K, Hedrick CC. Increased cholesterol content in gammadelta (γδ) T lymphocytes differentially regulates their activation. PLoS One 2013;8:e63746.
  25. Vu DM, Tai A, Tatro JB, Karas RH, Huber BT, Beasley D. γδT cells are prevalent in the proximal aorta and drive nascent atherosclerotic lesion progression and neutrophilia in hypercholesterolemic mice. PLoS One 2014;9:e109416.
  26. Zhang S, Kan X, Li Y, Li P, Zhang C, Li G, Du J, You B. Deficiency of γδT cells protects against abdominal aortic aneurysms by regulating phosphoinositide 3-kinase/AKT signaling. J Vasc Surg 2018;67:899-908.e1. https://doi.org/10.1016/j.jvs.2016.03.474
  27. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol 2009;27:485-517. https://doi.org/10.1146/annurev.immunol.021908.132710
  28. Nishida N, Aoki H, Ohno-Urabe S, Nishihara M, Furusho A, Hirakata S, Hayashi M, Ito S, Yamada H, Hirata Y, et al. High salt intake worsens aortic dissection in mice: involvement of IL (interleukin)-17a-dependent ECM (extracellular matrix) metabolism. Arterioscler Thromb Vasc Biol 2020;40:189-205. https://doi.org/10.1161/ATVBAHA.119.313336