Regulation of Immune Responses during Airway Inflammation

Abstract

Allergic asthma is refractory to corticosteroid treatment in up to 10% of patients and often leads to hospital admissions caused by respiratory viral and/ or bacterial infections. In these studies, I found that: 1) STAT6 inhibited innate γδ17 cell immune responses. STAT6 suppression of γδ17 cell function may provide one explanation for why asthmatic patients have significantly greater risk for invasive bacterial disease, including pneumonia, than nonasthmatic subjects. 2) A GLP-1R agonist, an FDA-approved agent currently used for Type II Diabetes, attenuated the type 2 immune response to RSV and attenuates RSV illness. The current availability of GLP-1R agonists for human treatment highlights the clinical significance of these studies as this therapy could be immediately transferrable to RSV disease. 3) PGI2, an FDA-approved agent currently used for pulmonary hypertension, protected against autoimmunity; enhanced Treg stability and function; rendered T effector cells more susceptible to Treg- mediated suppression; and promoted iTreg differentiation. PGI2 may therefore represent a novel treatment strategy for diseases that result from Treg dysregulation.