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.