PI3-Kinase δγ Catalytic Isoforms Regulate the Th-17 Response in Tuberculosis.

摘要: Although IL17A plays a protective role at the mucosal surface, when signaling becomes dysregulated, pathological response is locally induced. At early stages of Mycobacterium tuberculosis (M.tb) infection, contributes to granuloma formation and pathogen containment. In contrast, during disease progression, dysregulated hyperinflammatory drives tissue destruction through enhanced neutrophil recruitment. Cumulative research has implicated PI3-Kinase pathways as one most relevant in pathophysiology inflammation. Evidence shows that IL-17A secretion expansion Th17 population dependant signaling, with p110δ p110γ isoforms playing prominent role. The isoform promotes progression dampening response, preventing clearance gene, PIK3CG downregulated TB patients late-stage compared healthy controls, demonstrating an important modulatory for this TB. Conversely, induces release from pulmonary γδ T-cells, committed cells recruitment lung. Inhibiting not only suppresses cells, but it also inhibits cytokine production multiple T-helper cell types. Since increased levels are observed be localized lung compartments (BAL lymphocytes) comparison circulating levels, inhalable PI3Kδ inhibitor, which currently utilized inflammatory airway diseases characterized by over-secretion, may therapeutic option active disease.