Legumain Regulates Regulatory T Cells in Hypertension

HomeCirculation ResearchVol. 134, No. 1Legumain Regulates Regulatory T Cells in Hypertension No AccessEditorialRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessEditorialRequest AccessFull TextLegumain Regulates Regulatory T Cells in Hypertension Matthew R. Alexander and David G. Harrison Matthew R. AlexanderMatthew R. Alexander Correspondence to: Matthew R. Alexander, MD, PhD, Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, 2213 Garland Ave, MRBIV P415D, Nashville, TN 37232. Email E-mail Address: [email protected] https://orcid.org/0000-0003-4739-7204 Department of Medicine, Division of Clinical Pharmacology, and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN. Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, TN. Search for more papers by this author and David G. HarrisonDavid G. Harrison https://orcid.org/0000-0001-9363-6451 Department of Medicine, Division of Clinical Pharmacology, and Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN. Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, TN. Search for more papers by this author Originally published4 Jan 2024https://doi.org/10.1161/CIRCRESAHA.123.324010Circulation Research. 2024;134:30–32This article is a commentary on the followingCD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6FootnotesFor Sources of Funding and Disclosures, see page 32.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to: Matthew R. Alexander, MD, PhD, Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, 2213 Garland Ave, MRBIV P415D, Nashville, TN 37232. Email matt.alexander@vumc.orgREFERENCES1. He Y, Zou P, Lu J, Lu Y, Yuan S, Zheng X, Liu J, Zeng C, Liu L, Tang L, et al. CD4+ T cell legumain deficiency attenuates hypertensive damage via preservation of TRAF6.Circ Res. 2024; 134:9–29. doi: 10.1161/CIRCRESAHA.123.322835LinkGoogle Scholar2. Solberg R, Lunde NN, Forbord KM, Okla M, Kassem M, Jafari A. The mammalian cysteine protease legumain in health and disease.Int J Mol Sci. 2022; 23:15983. doi: 10.3390/ijms232415983CrossrefMedlineGoogle Scholar3. Lu Y, Hippen KL, Lemire AL, Gu J, Wang W, Ni X, Ranganathan P, Levine BL, Riley JL, June CH, et al. miR-146b antagomir-treated human Tregs acquire increased GVHD inhibitory potency.Blood. 2016; 128:1424–1435. doi: 10.1182/blood-2016-05-714535CrossrefMedlineGoogle Scholar4. Madhur MS, Elijovich F, Alexander MR, Pitzer A, Ishimwe J, Van Beusecum JP, Patrick DM, Smart CD, Kleyman TR, Kingery J, et al. Hypertension: do inflammation and immunity hold the key to solving this epidemic?Circ Res. 2021; 128:908–933. doi: 10.1161/CIRCRESAHA.121.318052LinkGoogle Scholar5. Ochs HD, Gambineri E, Torgerson TR. IPEX, FOXP3 and regulatory T-cells: a model for autoimmunity.Immunol Res. 2007; 38:112–121. doi: 10.1007/s12026-007-0022-2CrossrefMedlineGoogle Scholar6. Barhoumi T, Kasal DA, Li MW, Shbat L, Laurant P, Neves MF, Paradis P, Schiffrin EL. T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury.Hypertension. 2011; 57:469–476. doi: 10.1161/HYPERTENSIONAHA.110.162941LinkGoogle Scholar7. Sawant DV, Vignali DA. Once a Treg, always a Treg?Immunol Rev. 2014; 259:173–191. doi: 10.1111/imr.12173CrossrefMedlineGoogle Scholar8. Gackowska L, Michalkiewicz J, Helmin-Basa A, Klosowski M, Niemirska A, Obrycki L, Kubiszewska I, Wierzbicka A, Litwin M. Regulatory T-cell subset distribution in children with primary hypertension is associated with hypertension severity and hypertensive target organ damage.J Hypertens. 2019; 38:692–700. doi: 10.1097/hjh.0000000000002328CrossrefGoogle Scholar9. Alexander MR, Dale BL, Smart CD, Elijovich F, Wogsland CE, Lima SM, Irish JM, Madhur MS. Immune profiling reveals decreases in circulating regulatory and exhausted T cells in human hypertension.JACC Basic Transl Sci. 2023; 8:319–336. doi: 10.1016/j.jacbts.2022.09.007CrossrefMedlineGoogle Scholar10. Sun X, Feng Y, Gong C, Bao X, Wei Z, Chang L, Chen H, Xu B. Hypertension-driven regulatory T-cell perturbations accelerate myocardial ischemia-reperfusion injury.Hypertension. 2023; 80:2046–2058. doi: 10.1161/HYPERTENSIONAHA.123.20481LinkGoogle Scholar11. Stathopoulou C, Gangaplara A, Mallett G, Flomerfelt FA, Liniany LP, Knight D, Samsel LA, Berlinguer-Palmini R, Yim JJ, Felizardo TC, et al. PD-1 Inhibitory receptor downregulates asparaginyl endopeptidase and maintains foxp3 transcription factor stability in induced regulatory T cells.Immunity. 2018; 49:247–263.e7. doi: 10.1016/j.immuni.2018.05.006CrossrefMedlineGoogle Scholar12. Gillis EE, Belanger K, Abdelbary M, Mohamed R, Sun J, Brands MW, Sullivan JC. Splenectomy increases blood pressure and abolishes sex differences in renal T-regulatory cells in spontaneously hypertensive rats.Clin Sci (Lond). 2021; 135:2329–2339. doi: 10.1042/CS20210469CrossrefMedlineGoogle Scholar13. Freeley S, Cardone J, Günther SC, West EE, Reinheckel T, Watts C, Kemper C, Kolev MV. Asparaginyl endopeptidase (legumain) supports human th1 induction via cathepsin L-mediated intracellular C3 activation.Front Immunol. 2018; 9:2449. doi: 10.3389/fimmu.2018.02449CrossrefMedlineGoogle Scholar14. Li N, Liu C, Ma G, Tseng Y, Pan D, Chen J, Li F, Zeng X, Luo T, Chen S. Asparaginyl endopeptidase may promote liver sinusoidal endothelial cell angiogenesis via PI3K/Akt pathway.Rev Esp Enferm Dig. 2019; 111:214–222. doi: 10.17235/reed.2018.5709/2018CrossrefMedlineGoogle Scholar15. Meng X, Yang J, Dong M, Zhang K, Tu E, Gao Q, Chen W, Zhang C, Zhang Y. Regulatory T cells in cardiovascular diseases.Nat Rev Cardiol. 2015; 13:167–179. doi: 10.1038/nrcardio.2015.169CrossrefMedlineGoogle Scholar eLetters(0) eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate. Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page. Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesCD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6Yuhu He, et al. Circulation Research. 2024;134:9-29 January 5, 2024Vol 134, Issue 1 Advertisement Article Information Metrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.123.324010PMID: 38175912 Originally publishedJanuary 4, 2024 KeywordsEditorialshypertensioninflammationT-lymphocytesT lymphocytes, regulatoryPDF download Advertisement