Immune Profiling Reveals Decreases in Circulating Regulatory and Exhausted T Cells in Human Hypertension

Matthew R Alexander; Bethany L Dale; Charles D Smart; Fernando Elijovich; Cara E Wogsland; Sierra M Lima; Jonathan M Irish; Meena S Madhur

doi:10.1016/j.jacbts.2022.09.007

Immune Profiling Reveals Decreases in Circulating Regulatory and Exhausted T Cells in Human Hypertension

JACC Basic Transl Sci. 2023 Jan 4;8(3):319-336. doi: 10.1016/j.jacbts.2022.09.007. eCollection 2023 Mar.

Authors

Matthew R Alexander^{1

2

3

4}, Bethany L Dale^{4

5}, Charles D Smart⁴, Fernando Elijovich¹, Cara E Wogsland^{6

7}, Sierra M Lima⁸, Jonathan M Irish^{3

6

8}, Meena S Madhur^{1

2

3

4}

Affiliations

¹ Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
² Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, Tennessee, USA.
⁴ Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
⁵ Current affiliation: Pirche, Berlin, Germany.
⁶ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷ Current affiliation: KinN Therapeutics, Bergen, Norway.
⁸ Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Abstract

Evidence from nonhuman animal models demonstrates an important role for immune cells in hypertension, but immune cell changes in human hypertension are less clear. Using mass cytometry, we demonstrate novel and selective reductions in CCR10⁺ regulatory T cells (Tregs) and PD-1⁺CD57^-CD8⁺ memory T cells. RNA sequencing reveals that CCR10⁺ Tregs exhibit gene expression changes consistent with enhanced immunosuppressive function. In addition, CITE-Seq demonstrates that PD-1⁺CD57^-CD8⁺ memory T cells exhibit features of T-cell exhaustion. Taken together, these results provide novel evidence for decreases in anti-inflammatory and/or hypofunctional T-cell populations that may contribute to enhanced inflammation in human hypertension.

Keywords: hypertension; immunity; inflammation; lymphocytes; mass cytometry.

Abstract

Grants and funding