CD103 expression on DCs regulates the onset and severity of TH17 airway inflammation

Abstract

Abstract Pulmonary dendritic cells (DCs) drive TH17 immunopathological responses to foreign antigens, including Saccharopolyspora rectivirgula (SR), a causative agent of hypersensitivity pneumonitis (HP). More specifically, CD103+ DCs, a DC cell subset found in the lung, are associated with the induction of TH17 responses; however, this remains controversial, as they are also associated with regulatory activity. Furthermore, the importance and modulation of CD103 expression on DCs and T cells in homeostasis maintenance and the regulation of TH17 hypersensitivity responses is elusive. We aimed to verify whether modulation of CD103 expression is important in the onset and regulation of the TH17 hypersensitivity lung response in HP. Exposure to SR in Cd103−/− mice led to an exacerbation of the inflammatory response as early as 18h after the first exposure to SR. Using DC and T cell transfers experiments, we demonstrate that CD103 expression on DCs specifically (and not T cells) is crucial in regulating this TH17 response. Interestingly, we observed that SR exposure (in vivo and in vitro) reduces rapidly CD103 protein and mRNA expression by DCs. In conclusion, we demonstrate that CD103 expression by DCs at the onset of the TH17 inflammatory response is crucial for homeostasis maintenance and regulation of the TH17 hypersensitivity response, and that loss of CD103 expression following antigen exposure may be a new mechanism leading to homeostasis breakdown in the lung.