IL-25-responsive migratory iILC2s require BATF and stably convert to tissue-resident nILC2s

Abstract

Abstract Inflammatory ILC2s (iILC2s) are a transient subset of group-2 innate lymphoid cells that migrate to the lung shortly after helminth infection or IL-25 administration. Our recent findings identified the AP-1 factor BATF as the major transcriptional regulator required for iILC2 generation and function. Batf-deficient mice infected with the helminth Nippostrongylus brasiliensis display a selective defect in IL-25-mediated worm clearance and a loss of iILC2s but not nILC2s. This corresponds with the absence of early cytokine production by ILC2s in Batf-deficient mice, indicating the requirement of this transcription factor in ILC2 function. The fate of iILC2s is currently unknown as this subset of ILC2s is found only transiently in the lung following infection. Taking advantage of our finding that Arginase-1 (Arg1) expression can delineate tissue-resident nILC2 (Arg1+) and migratory iILC2 (Arg1−) populations, we used an Arg1 reporter mouse to address whether iILC2s could acquire an Arg1+ nILC2-like phenotype. Upon transfer into a congenic host, sorted Arg1− iILC2s acquired Arg1 expression and further adopted characteristics of nILC2s. These converted cells stably persisted after transfer indicating a potential long-term contribution of migratory iILC2s to the tissue-resident nILC2 pool in the lung.