Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells

Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that, driven by commensal fungi, a wave of CD45+CD103+RALDH+ cells migrates to the peripheral lymph nodes after birth. The arrival of these cells introduces high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directs the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH+ cells might serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in vitamin-A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs. [Display omitted] •Gut microbiota is required for secondary lymphoid organ development•Gut RALDH+ DCs move to peripheral lymph nodes after gut fungal colonization•These DCs initiate LN structural development via retinoic acid signaling•Neonatal lymphocytes are imprinted for gut homing by these DCs Gut microbiota promotes the development of secondary lymphoid organs. Here, Shi and colleagues demonstrate that CD45+CD103+RALDH+ dendritic cells in the gut respond to microbial colonization and migrate to the periphery. These DCs use retinoic acid signaling to initiate the lymph node cellularity increase and volume expansion.