Browsing by Author "Thomas, Christopher M."

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    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 Medicine
    Type 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.
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    Donation After Circulatory Arrest in Pancreas Transplantation: A Report of 10 Cases
    (Elsevier, 2017-12) Fridell, Jonathan A.; Mangus, Richard S.; Thomas, Christopher M.; Kubal, Chandrashekhar A.; Powelson, John A.; Surgery, School of Medicine
    Introduction Transplantation of pancreas allografts procured from donation after circulatory death (DCD) remains uncommon. This study reviews a series of pancreas transplants at a single center to assess the donor and recipient characteristics for DCD pancreas transplant and to compare clinical outcomes. Methods DCD procurement was performed with a 5-minute wait time from pronouncement of death to first incision. In 2 patients, tissue plasminogen activator was infused as a thrombolytic during the donor flush. All kidney grafts were placed on pulsatile perfusion. Results There were 606 deceased donor pancreas transplants, 596 standard donors and 10 DCD donors. Of the 10 DCD transplants, 6 were simultaneous pancreas-kidney and 4 were pancreas transplant alone. The average time from incision to aortic cannulation was less than 3 minutes. The median total ischemia time for the DCD grafts was 5.4 hours, compared with 8.0 hours for standard donors (P = .15). Median length of hospital stay was 7 days for both groups, and there were no episode of acute cellular rejection in the first year post-transplant for the DCD group (4.2 % for standard group, P = .65). There was no difference in early or late graft survival, with 100% graft survival in the DCD group up to 1 year post-transplant. Ten-year Kaplan-Meier analysis shows similar graft survival for the 2 groups (P = .92). Conclusions These results support the routine use of carefully selected DCD pancreas donors. There were no differences in graft function, postoperative complications, and early and late graft survival.