Female Spontaneously Hypertensive Rats Have a Compensatory Increase in Renal Regulatory T Cells in Response to Elevations in Blood Pressure

Tipton, Ashlee J.; Baban, Babak; Sullivan, Jennifer C.

doi:10.1161/hypertensionaha.114.03512

Cited by 82 publications

(90 citation statements)

References 35 publications

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“…Indeed, a recent report found that Ang II-induced increases in cardiac IL-17A was derived primarily from infiltrating γδT cells, not CD4 + T cells, and deletion of γδT cell resulted in protection from Ang II-induced cardiac injury 67 . Consistent with this notion that Th17 cells are not critical in BP control, our group recently published that attenuating age-related increases in BP in SHR was not associated with significant changes renal Th17 cells 68 , however, we did not assessγδT cells. Therefore, γδT cells may be more critical in mediating increases in BP than Th17 cells, however, to date, there are not any studies in the literature that have employed adoptive transfer of isolated Th17 cells to conclusively link them to BP regulation.…”

Section: Th17 Cells and Hypertensionsupporting

confidence: 68%

“…We have also shown that similar to what is observed in males, increases in BP are associated with increases in renal T cell infiltration in females. Female SHR have significantly more T cells in their kidneys than normotensive WKY and increasing BP in female SHR increases renal T cell counts 68 . Chronic nitric oxide synthase inhibition using L-NAME also increases BP in male and female SHR and this increase in BP was associated with increases in renal T cells in both sexes, however, female SHR exhibited greater increases in Th17 cells and greater decreases in Tregs than males 20 .…”

Section: Sex Differences In Inflammation In Hypertensionmentioning

confidence: 95%

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Sex Differences in T Cells in Hypertension

Tipton

Sullivan

2014

Clinical Therapeutics

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Purpose Hypertension is a major risk factor for the development of cardiovascular disease, stroke and end-organ damage. There is a sex difference in blood pressure (BP) that begins in adolescence and continues into adulthood, where men have a higher prevalence of hypertension compared to women until the sixth decade of life. Less than 50% of hypertensive adults in the United States taking medication manage to control their BP to recommended levels using current therapeutic options, and women are more likely than men to have uncontrolled high BP. This is despite the fact that more women compared to men are aware that they have hypertension and women are more likely to seek treatment for the disease. Novel therapeutic targets need to be identified in both sexes to increase the percentage of hypertensive individuals with controlled BP. The purpose of this article is to review the available literature on the role of T cells in BP control in both sexes, and the potential therapeutic application/implications of targeting immune cells in hypertension. Methods A search of PUBMED was conducted to determine the impact of sex and gender on T cell-mediated control of BP. The search terms included sex, gender, estrogen, testosterone, inflammation, T cells, T regulatory cells, Th17 cells, hypertension and blood pressure. Additional data were included from our laboratory examining cytokine expression in the kidney of male and female SHR and differential genes expression in both the renal cortex and mesenteric arterial bed of male and female SHR. Findings There is a growing basic science literature regarding the role of T cells in the pathogenesis of hypertension and BP control, however, the majority of this literature has been performed exclusively in males despite the fact that both men and women develop hypertension. There is increasing evidence that while T cells also mediate BP in females, there are distinct differences in both the T cell profile and the functional impact of “male” vs. “female” T cells on cardiovascular health, although more work is needed to better define the relative impact of different T cell subtypes on BP in both sexes. Implications The challenge now is to fully understand the molecular mechanisms by which the immune system regulates BP and how the different components of the immune system interact so that specific mechanisms can be targeted therapeutically without compromising natural immune defenses.

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Section: Th17 Cells and Hypertensionsupporting

confidence: 68%

Section: Sex Differences In Inflammation In Hypertensionmentioning

confidence: 95%

Sex Differences in T Cells in Hypertension

Tipton

Sullivan

2014

Clinical Therapeutics

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“…In a recent study, gonadectomy of male and female SHRs increased proinflammatory cells in both sexes. 59 However, we found that Cyp1b1 gene disruption or castration of Cyp1b1 +/+ mice attenuated Ang II-induced infiltration of CD4 + T-lymphocytes and treatment with 6β-OHT restored renal accumulation of CD4 + T-cells in Cyp1b1 −/− mice but failed to do so in castrated mice. These results suggest that 6β-OHT is insufficient to restore Ang II-induced infiltration of CD4 + T-cells, and testosterone and/or its metabolite DHT is required for accumulation of these cells in castrated mice.…”

Section: Discussionmentioning

confidence: 62%

6β-Hydroxytestosterone, a Cytochrome P450 1B1-Testosterone–Metabolite, Mediates Angiotensin II–Induced Renal Dysfunction in Male Mice

et al. 2016

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6β-hydroxytestosterone, a cytochrome P450 1B1-derived metabolite of testosterone, contributes to the development of angiotensin II-induced hypertension and associated cardiovascular pathophysiology. In view of the critical role of angiotensin II in the maintenance of renal homeostasis, development of hypertension and end organ damage, this study was conducted to determine the contribution of 6β-hydroxytestosterone to angiotensin II actions on water consumption and renal function in male Cyp1b1+/+ and Cyp1b1−/− mice. Castration of Cyp1b1+/+ mice or Cyp1b1−/− gene disruption minimized the angiotensin II-induced increase in water consumption, urine output, proteinuria, and sodium excretion and decreases in urine osmolality. 6β-hydroxytestosterone did not alter angiotensin II-induced increases in water intake, urine output, proteinuria, and sodium excretion or decreases in osmolality in Cyp1b1+/+ mice, but restored these effects of angiotensin II in Cyp1b1−/− or castrated mice Cyp1b1+/+ mice. Cyp1b1 gene disruption or castration prevented angiotensin II-induced renal fibrosis, oxidative stress, inflammation, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, and angiotensin converting enzyme. 6β-hydroxytestosterone did not alter angiotensin II-induced renal fibrosis, inflammation, oxidative stress, urinary excretion angiotensinogen, expression of angiotensin II type 1 receptor, or angiotensin converting enzyme in Cyp1b1+/+ mice; however, in Cyp1b1−/− or castrated mice Cyp1b1+/+ mice, it restored these effects of angiotensin II. These data indicate that 6β-hydroxytestosterone contributes to increased thirst, impairment of renal function, and end organ injury associated with angiotensin II-induced hypertension in male mice and that cytochrome P450 1B1 could serve as a novel target for treating renal disease and hypertension in males.

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“…Also of great interest, the authors describe the impact of the sex of the T-cell donors on angiotensin II-induced hypertension. The authors go on to demonstrate changes in T-cell expression in the ageing female brain and how oestrogen may impact regions of the brain involved in blood pressure regulation (Tipton et al 2014). Overall, this review provides a picture of how the adaptive immune system is involved in blood pressure regulation by angiotensin II and how sex and sex hormones influence this interaction.…”

Section: Sex Hormone Effects On Autonomic and Endothelial Functionmentioning

confidence: 99%

Sex hormone effects on autonomic and endothelial function

Stachenfeld¹

2016

Experimental Physiology

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Female Spontaneously Hypertensive Rats Have a Compensatory Increase in Renal Regulatory T Cells in Response to Elevations in Blood Pressure

Cited by 82 publications

References 35 publications

Sex Differences in T Cells in Hypertension

Sex Differences in T Cells in Hypertension

6β-Hydroxytestosterone, a Cytochrome P450 1B1-Testosterone–Metabolite, Mediates Angiotensin II–Induced Renal Dysfunction in Male Mice

Sex hormone effects on autonomic and endothelial function

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