Sex-Specific T-Cell Regulation of Angiotensin II–Dependent Hypertension
| Autor: | Wei Zheng, Kathryn Sandberg, Meredith Hay, Jason G. Umans, Robert C. Speth, Xiangjun Li, Xie Wu, Monan Angela Zhang, Shannon E. Dunn, Hong Ji, Jun Liu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Mean arterial pressure medicine.medical_specialty T-Lymphocytes T cell Adipose tissue Blood Pressure Adaptive Immunity Biology Article Mice Sex Factors Immune system Heart Rate Internal medicine Renin–angiotensin system Internal Medicine medicine Animals Homeodomain Proteins Mice Knockout Kidney Tumor Necrosis Factor-alpha Angiotensin II Interleukin-17 Interleukin-10 Disease Models Animal Blood pressure medicine.anatomical_structure Endocrinology Hypertension Female |
| Zdroj: | Hypertension. 64:573-582 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.114.03663 |
| Popis: | 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 −/− -F, 135±2.1 versus Rag1 −/− -M, 141±3.8). Peak mean arterial pressure was 13 mm Hg higher after adoptive transfer of male (CD3 M →Rag1 −/− -M) versus female (CD3 F →Rag1 −/− -M) T cells. CD3 M →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 CD3 F →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. |
| Databáze: | OpenAIRE |
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