Abstract

Dysbiosis in the gut microbiota affects several systemic diseases, possibly by driving the migration of perturbed intestinal immunocytes to extraintestinal tissues. Combining Kaede photoconvertible mice and single-cell genomics, we generated a detailed map of migratory trajectories from the colon, at baseline, and in several models of intestinal and extraintestinal inflammation. All lineages emigrated from the colon in an S1P-dependent manner. B lymphocytes represented the largest contingent, with the unexpected circulation of nonexperienced follicular B cells, which carried a gut-imprinted transcriptomic signature. T cell emigration included distinct groups of RORγ+ and IEL-like CD160+ subsets. Gut inflammation curtailed emigration, except for dendritic cells disseminating to lymph nodes. Colon-emigrating cells distributed differentially to distinct sites of extraintestinal models of inflammation (psoriasis-like skin, arthritic synovium, and tumors). Thus, specific cellular trails originating in the gut and influenced by microbiota may shape peripheral immunity in varied ways.

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