Complex role of STAT6 in allergic airway inflammation (39.11)

Abstract

Abstract STAT6 plays a critical role in Th2 cell differentiation and in allergic lung inflammation. Using a chimeric mouse model, we observed alternative lung pathology in STAT6 KO mice even when WT bone marrow or Th2 cells were provided. Thus, we hypothesized that STAT6 contributes to inflammation in a complex manner. To detail STAT6 function, WT and STAT6 KO mice were subjected to OVA priming and challenges. Broncho-alveolar lavage (BAL) cell composition, lung histology, and FACS analysis of digested lungs were assessed 48h after the last challenge. As expected, eosinophils composed a majority of BAL cells in WT mice and less than 2% in STAT6 KO mice. The OVA-induced inflammation in STAT6 KO lungs was composed mainly of macrophages with small fractions of neutrophils and lymphocytes. The OVA-treated WT lungs showed strong although divergent expression of F4/80, Mac-2, and CD11b molecules; this was significantly reduced in STAT6 KO mice. However, the numbers of dendritic cells, B cells, CD4+ and CD8+ T cells in the lungs of OVA-treated mice were unaffected by STAT6 deficiency. Interestingly, STAT6 KO mice showed enhanced basal airway reactivity to methacholine and numbers of Mac-2+ cells as compared to WT mice, suggesting that STAT6 deficiency altered lung homeostasis. Taken together, our studies demonstrate STAT6-dependent and –independent features of asthma phenotype which may impact treatments targeting STAT6. (AI38985)