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Browsing by Author "Abney, Masako"
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Item CFTR negatively reprograms Th2 cell responses, and CFTR potentiation restrains allergic airway inflammation(American Society for Clinical Investigation, 2025-03-25) Rusznak, Mark; Thomas, Christopher M.; Zhang, Jian; Toki, Shinji; Zhou, Weisong; Abney, Masako; Yanda, Danielle M.; Norlander, Allison E.; Hodges, Craig A.; Newcomb, Dawn C.; Kaplan, Mark H.; Peebles, R. Stokes, Jr.; Cook, Daniel P.; Anatomy, Cell Biology and Physiology, School of MedicineType 2 inflammatory diseases, including asthma, sinusitis, and allergic bronchopulmonary aspergillosis, are common in cystic fibrosis (CF). CD4+ Th2 cells promote these diseases through secretion of IL-4, IL-5, and IL-13. Whether the CF transmembrane conductance regulator (CFTR), the mutated protein in CF, has a direct effect on Th2 development is unknown. Using murine models of CFTR deficiency and human CD4+ T cells, we show that CD4+ T cells expressed Cftr transcript and CFTR protein following activation. Loss of T cell CFTR expression increased Th2 cytokine production compared with control cells. Mice with CFTR-deficient T cells developed increased allergic airway disease to Alternaria alternata extract compared with control mice. Culture of CFTR-deficient Th2 cells demonstrated increased IL-4Rα expression and increased sensitivity to IL-4 with greater induction of GATA3 and IL-13 compared with control Th2 cell cultures. The CFTR potentiator ivacaftor reduced allergic inflammation and type 2 cytokine secretion in bronchoalveolar lavage of humanized CFTR mice following Alternaria alternata extract challenge and decreased Th2 development in human T cell culture. These data support a direct role of CFTR in regulating T cell sensitivity to IL-4 and demonstrate a potential CFTR-specific therapeutic strategy for Th2 cell-mediated allergic disease.Item Prostaglandin I2 Therapy Promotes Regulatory T Cell Generation in Patients with Pulmonary Arterial Hypertension(American Thoracic Society, 2023) Norlander, Allison E.; Abney, Masako; Cephus, Jacqueline-Yvonne; Roe, Caroline E.; Irish, Jonathan M.; Shelburne, Nicholas J.; Newcomb, Dawn C.; Hemnes, Anna R.; Peebles, R. Stokes, Jr.; Anatomy, Cell Biology and Physiology, School of MedicineItem Reply to Yasuma et al.(American Thoracic Society, 2023) Norlander, Allison E.; Abney, Masako; Cephus, Jacqueline-Yvonne; Roe, Caroline E.; Irish, Jonathan M.; Shelburne, Nicholas J.; Newcomb, Dawn C.; Hemnes, Anna R.; Peebles, R. Stokes, Jr.; Medicine, School of Medicine