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Aged Female HV1 ‐/‐ DAHL Salt‐Sensitive Rats Develop a Pro‐Inflammatory T‐Cell Profile
Author(s) -
Ralph Erica,
Sullivan Jennifer,
O'Connor Paul
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb769
Subject(s) - medicine , endocrinology , immune system , flow cytometry , pathogenesis , blood pressure , phenotype , inflammation , cd8 , proteinuria , lupus nephritis , kidney , chemistry , biology , immunology , gene , disease , biochemistry
Th17 cells are pro‐inflammatory cells that have been implicated in the pathogenesis of several autoimmune diseases and more recently linked to the progression of hypertension and related end‐organ damage. Hv1 is a voltage‐gated H + channel highly expressed in immune cells, including T cells. Hv1‐knockout mice have been reported to develop an autoimmune phenotype, including greater activation of circulating CD4 + T‐cells and development of nephritis in aged mice, which is more pronounced in females. We have recently developed a Hv1 ‐/‐ rat on the Dahl salt‐sensitive rat (SS) genetic background. The goal of this study was to determine whether T‐cells are activated in male and female rats lacking Hv1 and whether this is associated with alterations in blood pressure and/or renal injury. Flow cytometry analysis did not identify a difference in CD4 + T‐cells or Th17 cells in whole blood from 12 week old female SS and Hv1 ‐/‐ SS rats fed either a low (0.4%) or high (8%) NaCl diet for 14 days prior to sacrifice ( TABLE ). The number of circulating pro‐inflammatory T‐cells was significantly increased in aged Hv1 ‐/‐ rats, with T‐cell activation being more pronounced in females ( TABLE; p=0.005 ). Despite significantly more circulating Th17 cells in aged female Hv1 ‐/‐ rats, blood pressure (telemetry) was not different between the sexes at 40‐42 weeks of age (162±7mmHg; n=5 and 158±8mmHg; n=6 in females and males, respectively) and renal injury was significantly worse in male Hv1 ‐/‐ rats (proteinuria 61±24mg/day in females vs 165±32mg/day in males; p=0.014). We conclude that aged female Hv1 ‐/‐ SS rats develop a more activated circulating inflammatory T‐cell profile compared to males but that this is not associated with higher blood pressure or worse renal injury.12 wk WT Female 0.4% LS 12 wk WT female 8% HS 12 wk KO Female 0.4% LS 12 wk KO female 8% HS 42 wk KO female 0.4% LS 42 wk KO male 0.4% LSCD4 + cells (% CD3 + ) 38±1 50±3 37±2 40±4 70±2 52±1Th17 cells (% CD3 + CD4 + ) 21±5 27±7 32±2 24±8 55±1 43±1