Sex-specific T-cell regulation of angiotensin II-dependent hypertension

Hong Ji, Wei Zheng, Xiangjun Li, Jun Liu, Xie Wu, Monan Angela Zhang, Jason G. Umans, Meredith Hay, Robert C. Speth, Shannon E. Dunn, Kathryn Sandberg

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Studies suggest T cells modulate arterial pressure. Because robust sex differences exist in the immune system and in hypertension, we investigated sex differences in T-cell modulation of angiotensin II-induced increases in mean arterial pressure in male (M) and female (F) wild-type and recombination- activating-gene-1-deficient (Rag1-/-) mice. Sex differences in peak mean arterial pressure in wild-type were lost in Rag1-/-) mice (mm Hg: wild-type-F, 136±4.9 versus wild-type-M, 153±1.7; P<0.02; Rag1-/-) -F, 135±2.1 versus Rag1-/-) -M, 141±3.8). Peak mean arterial pressure was 13 mm Hg higher after adoptive transfer of male (CD3M→Rag1-/-) -M) versus female (CD3F→Rag1-/-) -M) T cells. CD3M→ Rag1-/-) -M mice exhibited higher splenic frequencies of proinflammatory interleukin-17A (2.4-fold) and tumor necrosis factor-α (2.2-fold)-producing T cells and lower plasma levels (13-fold) and renal mRNA expression (2.4- fold) of interleukin-10, whereas CD3F→Rag1 -/-) -M mice displayed a higher activation state in general and T-helper- 1-biased renal inflammation. Greater T-cell infiltration into perivascular adipose tissue and kidney associated with increased pressor responses to angiotensin II if the T cell donor was male but not female and these sex differences in T-cell subset expansion and tissue infiltration were maintained for 7 to 8 weeks within the male host. Thus, the adaptive immune response and role of pro- And anti-inflammatory cytokine signaling in hypertension are distinct between the sexes and need to be understood to improve therapeutics for hypertension-associated disease in both men and women.

Original languageEnglish (US)
Pages (from-to)573-582
Number of pages10
JournalHypertension
Volume64
Issue number3
DOIs
StatePublished - Sep 2014

Keywords

  • Angiotensins
  • Hypertension
  • Interleukin 10
  • Interleukin 17
  • Sex characteristics
  • T-lymphocytes
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Ji, H., Zheng, W., Li, X., Liu, J., Wu, X., Zhang, M. A., Umans, J. G., Hay, M., Speth, R. C., Dunn, S. E., & Sandberg, K. (2014). Sex-specific T-cell regulation of angiotensin II-dependent hypertension. Hypertension, 64(3), 573-582. https://doi.org/10.1161/HYPERTENSIONAHA.114.03663