Type I IFN signaling controls T lymphocyte transmigration into the airways (102.10)

Abstract

Abstract Our current understanding of how T lymphocytes enter the airways in response to respiratory tract infections is limited. Here we show a role for type I interferon (IFN) signaling in regulating T lymphocyte transmigration into the airway mucosa. IFNα receptor (IFNAR) deficiency led to a reduction in the number of T lymphocytes that entered the airways but not the lung parenchyma. This effect was mediated both at the T lymphocyte and epithelial cell level. IFNAR-deficient airway epithelial cells failed to express the chemoattractants CCL3-5, CCL8 and CXCL9-11, and did not up-regulate the adhesion molecules ICAM1 and VCAM1. Lack of IFNAR signaling on T lymphocytes impaired Ly-6C expression and lymphocyte function-associated antigen-1 (LFA-1) clustering, which resulted in reduced cell adhesion. Finally, we show that IFNAR-deficiency inhibited T lymphocyte recruitment to the airways during respiratory syncytial virus (RSV) infection.