Tu101 - Male Pups Have Increased Allergen and RSV-Induced Airway Inflammation After in Utero Allergen Exposure

Jacqueline Cephus – Medicine – Vanderbilt University Medical Center; Shelby Kuehnle – Medicine – Vanderbilt University Medical Center; Emely Henriquez Pilier – Pathology, Microbiology, and Immunology – Vanderbilt University; Andrew Peebles – Medicine – Vanderbilt University Medical Center; Allison Norlander – Medicine – Vanderbilt University Medical Center; Stokes Peebles – Medicine – Vanderbilt University Medical Center; Dawn Newcomb – Medicine – Vanderbilt University Medical Center

Abstract Text: As children, males have a higher incidence and prevalence of asthma compared to females at a 2:1 ratio. Maternal asthma is a risk factor for childhood asthma; however, it remains unclear whether maternal asthma contributes to the sex disparity in childhood asthma. We hypothesized that, following in utero exposure to allergen, male offspring would have decreased Treg stability and function, leading to increased allergic airway inflammation. To test our hypothesis, we intranasally administered house dust mite (HDM) allergen or vehicle to pregnant Foxp3 fate mapping females (Foxp3EGFP-Cre Rosa26YFP/YFPIl13TdTomato/TdTomato) that were mated with Foxp3EGFP-CreRosa26YFP/YFP males. At 3 weeks of age, male and female pups (Foxp3EGFP-CreRosa26YFP/YFPIl13WT/TdTomato) were intranasally challenged with mock or RSV 01/2-20 clinical isolate (3x107 PFU/ml). Lungs were harvested from pups 7 days post infection. Mock challenged males exposed in utero to HDM had increased IL-13+ CD4 T cells, increased ex-Tregs (Foxp3 GFP-YFP+), and decreased current Tregs (Foxp3 GFP+YFP+) compared to mock challenged, in utero HDM exposed female pups or in utero PBS exposed pups. Additionally, male pups infected with RSV had increased IL-13+ CD4 T cells, increased ex-Tregs, and decreased current Tregs compared to in utero HDM exposed female pups. Bronchoalveolar lavage (BAL) fluid showed increased eosinophils in male pups exposed in utero to HDM following RSV infection compared to female challenged pups. Combined, these results show sex differences in airway inflammation and Treg numbers following in utero exposure to allergen, providing a potential mechanism for the sex disparity in childhood asthma prevalence and severity.