Single-cell analysis of recruited ILC2 cell fate during transition from circulation to establishment of tissue residency

Circulating group 2 innate lymphoid cells (ILC2s) often serve as a first line of defense against infection prior to local expansion of lung-resident ILC2s. The fate of circulating ILC2s and their relationship with lung-resident ILC2s is not well understood. Using reporter mice in combination with single-cell RNA sequencing (scRNA-seq) and Cellular Indexing of Transcriptomes and Epitopes sequencing (CITE-seq), the fate of circulatory ILC2s was followed during the course of primary Nippostrongylus brasiliensis helminth infection. Circulating ILC2s rapidly acquire tissue-resident gene expression upon arrival to the lung. This transition occurs primarily as the cells enter the parenchyma from the vasculature. Despite acquiring a lung-resident phenotype by the peak of the immune response, these converted ILC2s retain some unique gene expression related to their intestinal origins which correlate with enhanced functionality. Findings provide insight into the tissue adaptation of circulatory ILC2s during recruitment to the lung and establish their contribution to the lung-resident ILC2 population.