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. 2025 May 23;121(5):817-831.
doi: 10.1093/cvr/cvaf042.

Beta 2 adrenergic receptor gene methylation activates innate lymphoid cells to drive hypertension in lymphocyte deficient hosts

Wei Chen  1 , Sara Perrotta  2 , Liang Xiao  3 , Lorenzo Carnevale  2 , Marwa A Abd-ElDayem  1   4 , Elizabeth M Hennen  1 , Luis Miguel Rivera-Medina  1 , David M Patrick  1 , Mingfang Ao  1 , Fabio Pallante  2 , Azzurra Zonfrilli  5 , Shilin Zhao  6 , Agnese Migliaccio  2 , Lan Lan  3 , Stefania Fardella  2 , Giuseppe Sciumè  5 , Francesco Mastroiacovo  2 , Giuseppe Lembo  2   5 , Daniela Carnevale  2   7 , David G Harrison  1
Affiliations

Beta 2 adrenergic receptor gene methylation activates innate lymphoid cells to drive hypertension in lymphocyte deficient hosts

Wei Chen et al. Cardiovasc Res. .

Abstract

Aims: T cells contribute to hypertension; however, hypertension occurs in settings of T cell deficiency.

Methods and results: We studied two colonies of T/B cell-deficient RAG-1-/- mice with disparate responses to angiotensin II, being one protected from blood pressure increase and the other one responsive. This difference depends on the capability of hypertensive RAG-1-/- mice to expand natural killer and innate lymphoid cells (NK/ILCs) that produce pro-hypertensive cytokines. This process is regulated by the DNA methylation status of the β2 adrenergic receptor (β2-AdR). Angiotensin II caused blood pressure elevation in T and NK/ILCs-deficient mice only when either T or NK/ILCs cells were adoptively reconstituted. Additional studies showed NK cell expansion in humans that underwent B cell depletion, and this was augmented in those with hypertension.

Conclusions: These findings illustrate that the modulation of NK/ILCs activation by adrenergic signalling governs an escape mechanism in lymphocyte-deficient host, enabling the development of hypertension.

Keywords: Adoptive transfer; Angiotensin II; Beta 2 adrenergic receptor; Hypertension; IL-17A; Innate lymphoid cells; Methylation; Natural killer cells.

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Conflict of interest statement

Conflict of interest: none declared.

References

    1. Norlander AE, Madhur MS, Harrison DG. The immunology of hypertension. J Exp Med 2018;215:21–33. - PMC - PubMed
    1. Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ, Harrison DG. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension 2010;55:500–507. - PMC - PubMed
    1. Saleh MA, Norlander AE, Madhur MS. Inhibition of interleukin 17-A but not interleukin-17F signaling lowers blood pressure and reduces end-organ inflammation in angiotensin II-induced hypertension. JACC Basic Transl Sci 2016;1:606–616. - PMC - PubMed
    1. Kamat NV, Thabet SR, Xiao L, Saleh MA, Kirabo A, Madhur MS, Delpire E, Harrison DG, McDonough AA. Renal transporter activation during angiotensin-II hypertension is blunted in interferon-γ−/− and interleukin-17A−/− mice. Hypertension 2015;65:569–576. - PMC - PubMed
    1. Nguyen H, Chiasson VL, Chatterjee P, Kopriva SE, Young KJ, Mitchell BM. Interleukin-17 causes rho-kinase-mediated endothelial dysfunction and hypertension. Cardiovasc Res 2013;97:696–704. - PMC - PubMed

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