Circulatory ILC2 convert and persist as part of the long-term tissue-resident pool after infection [Congenic Transfer]

The fate of these circulating ILC2 and their contribution to the long-term lung-resident ILC2 pool is not understood. Using reporter mice in combination with single cell RNA sequencing (scRNA-seq) and novel applications of Cellular Indexing of Transcriptomes and Epitopes sequencing (CITE-seq), we assessed vascular and parenchymal ILC2 populations during helminth infection and the fate of circulatory ILC2.

These studies revealed that circulating ILC2 rapidly convert to a tissue-resident phenotype upon arrival in the lung. Once converted, former circulating ILC2 become largely indistinguishable from lung-resident ILC2 over time. Key gene expression retained by converted ILC2 at the peak of the tissue-resident ILC2 response was related to maintained IL-25-responsiveness and unique cytokine potential.