The Lymph Nodes Draining The Small Intestine And Colon Are Anatomically Separate And Immunologically Distinct

Dendritic cells (DCs) in the small intestine (SI) and colon are fundamental to direct intestinal immune responses; they migrate to the mesenteric lymph nodes (MLN) and prime T cells. Using photoconvertable Kaede mice we demonstrate anatomical segregation of lymphatic drainage from the intestine, specifically that DCs from the SI and colon migrate to different nodes within the MLN, here called the SI draining sMLN and colon draining cMLN. As a consequence, the different frequencies of phenotypically and functionally distinct DC subsets observed in the SI and colon are reflected among the DCs in the sMLN and cMLN. Consistent with the SI’s function in absorbing food, fed antigen is presented only in the sMLN, but not the cMLN. Furthermore, the levels of expression of CCR9 and α4β7 are increased on T cells in the sMLN compared to the cMLN. DCs from the cMLN and colon are unable to metabolise vitamin A to retinoic acid; thus DCs may contribute to the differential expression of tissue homing markers observed in the sMLN and cMLN. In summary, the sMLN and cMLN and the DCs that migrate to these lymph nodes are anatomically and immunologically separate. By separately analyzing the appropriate nodes of the mesenteric chain, we have identified changes in cell populations that have previously been missed. This non-overlapping lymphatic drainage from the SI and colon to distinct parts of the MLN provides a mechanism by which immune responses in these functionally, anatomically, and immunologically specialised tissues can be independently controlled.