Type I regulatory (Tr1) cells contribute to immune suppression in the context of chronic infection, autoimmunity, and transplant tolerance. However, their physiological relevance in the resolution of acute respiratory infection is not understood. Here, we identify Tr1 cells accumulating in the lung parenchyma during resolution of the response to sublethal influenza A virus infection in mice. Tr1 cells were dependent on IL-27Ra; and in their absence recovery from IAV-induced weight loss is impaired. Notably, these Tr1 cells did not necessarily co-express the typical Tr1 markers LAG-3 and CD49b, with four distinct populations of Tr1 cells apparent in the lungs. Each population was suppressive and were differentially dependent on IL-10 to mediate suppression. Transcriptional analysis revealed a core Tr1 gene signature in each population and distinct expression profiles indicative of different states of activation and differentiation. Finally, sort-transfer experiments indicated non-linear plasticity between these subsets of Tr1 cells. Together, these data support Tr1 cells contributing to the resolution of acute inflammation and define novel Tr1 cell phenotypes in acute infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.