Central Role of T Helper 17 Cells in Chronic Hypoxia-Induced Pulmonary Hypertension.
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Inflammation is a prominent pathologic feature in pulmonary arterial hypertension as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4(+) T cells are required for initiating and maintaining inflammation, suggesting these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension.To test the hypothesis that CD4(+) T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension.We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 weeks) in wild-type mice and recombination-activating gene 1 knock-out mice (RAG1(-/-), lack mature T and B cells). Separate sets of mice were adoptively transferred with CD4(+), CD8(+), or T helper 17 cells prior to normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets.RAG1(-/-) mice had diminished right ventricular systolic pressure and arterial remodeling compared to wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4(+), but not CD8(+) T cells, restored the hypertensive phenotype in RAG1(-/-) mice. Interestingly, RAG1(-/-) mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4(+) cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia.T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension.Copyright © 2016, American Journal of Physiology-Lung Cellular and Molecular Physiology.
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