A dynamic atlas of immunocyte migration reveals specific populations of gut-imprinted cells in distal tissues

Dysbiosis in the gut microbiota impacts several systemic diseases. One possible mechanism is the migration of perturbed intestinal immunocytes to extra-intestinal tissues. Combining the Kaede photoconvertible mouse model and single-cell genomics, we generated a detailed map of migratory trajectories from the colon, at baseline and during intestinal and extra-intestinal inflammation. All colonic lineages emigrated from the colon in an S1P-dependent manner, dominated by B lymphocytes with a large continuous circulation of follicular B cells, which carried a gut-imprinted transcriptomic signature. T cell emigration was more selective, with distinct groups of RORg+ cells and IEL-like CD160+ T cells in the spleen. Gut inflammation curtailed emigration, except for DCs disseminating to lymph nodes. Colon emigrating cells distributed differentially to tumor, skin inflammation, or arthritic synovium, the former dominated by myeloid cells in a chemokine-dependent manner. These results thus reveal specific cellular trails originating in the gut, influenced by microbiota, which can shape peripheral immunity. Overall design: We investigated the transcriptional status of colon-origin migratory immunocytes and compared it to local cells. To do so we used 7-week-old female Kaede.B6 mice, and sorted splenic CD45+ Kaede green and CD45+ Kaede red from the same mice 24hr, 48hr and 72hr post-photoconversion of the descending colon. Each sample was tagged with DNA-coded anti-CD45 hashtag antibodies (BioLegend) post-sort. Cells were encapsulated using the Chromium Single Cell 5' v3 platform (10X Genomics).