Background:Interleukin (IL)-22 is a cytokine involved in tissue protection and repair following lung pathologies.Interferon (IFN)-λcytokines displayed similar properties during viral infection and a synergy of action betweenthese two players has been documented in the intestine. We hypothesize that duringPseudomonas aeruginosachallenge, IL-22 up-regulates IFN-λand that IFN-λexhibits protective functions duringPseudomonas aeruginosaacute pneumonia model in mice.Methods:Using an in vitro human alveolar epithelial cell line A549, we assessed the ability of IL-22 to enhanceIFN-λexpression during infection. IFN-λprotective function was evaluated in an acute mouse pneumonia model.Results:Wefirst demonstrated in murine lungs that only type-II alveolar cells express IL-22 receptor and that IL-22 treatment of A549 cell line up-regulates IFN-λexpression. In a murine acute pneumonia model, IL-22 ad-ministration maintained significant IFN-λlevels in the broncho-alveolarfluids whereas IL-22 neutralizationabolished IFN-λup-regulation. In vivo administration of IFN-λduringPseudomonas aeruginosapneumonia im-proves mice outcome by dampening neutrophil recruitment and decreasing epithelium damages.Discussion:We show here that IL-22 regulates IFN-λlevels duringPseudomonas aeruginosapneumonia.