IMMUNE CELL BALANCE IN CHRONIC HYPOXIA INDUCED PULMONARY HYPERTENSION

Abstract

Chronic hypoxia (CH), caused by sleep apnea, chronic obstructive pulmonary disease, or high-altitude exposure, leads to pulmonary hypertension (PH). The pathogenesis of CH-induced PH has a number of hallmarks, including phenotypic changes in the pulmonary smooth muscle cells, arterial wall thickening, enhanced vasoreactivity, and inflammation around the pulmonary arteries. Utilizing a T regulatory (Treg) cell lineage tracking mouse model, this dissertation sought to further establish the importance of Treg and T helper 17 (TH17) cell balance in CH-induced PH. We demonstrated that Treg number and suppressive capacity decrease, TH17 cells increase, and Treg-to-TH17 cell transition occurs following exposure to hypoxia. We also show evidence that inducing tolerance to collagen type V (col V), a known self-antigen, attenuates indices of CH-induced PH. Altogether, this work further elucidates the mechanisms of the inflammatory response and possible therapeutic targets for preventing and treating CH-induced PH