The lymph nodes draining the small intestine and colon are anatomically separate and immunologically distinct

Abstract

Dendritic cells (DCs) in the small intestine (SI) and colon are fundamental to direct intestinal immune responses; they migrate to the mesenteric lymph nodes (MLNs) and prime T cells. 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 sMLN and cMLN. As a consequence, different frequencies of 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 in the sMLN, but not in the cMLN. Furthermore, the levels of expression of CCR9 and α4β7 are increased on T cells in the sMLN compared with the cMLN. DCs from the cMLN and colon are unable to metabolize vitamin A to retinoic acid (RA); 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 LNs are anatomically and immunologically separate. This segregation allows immune responses in the SI and colon to be controlled independently.

Activation of Plasmacytoid Dendritic Cells in Colon-Draining Lymph Nodes during Citrobacter rodentium Infection Involves Pathogen-Sensing and Inflammatory Pathways Distinct from Conventional Dendritic Cells

“…Along with the detailed analyses of Houston et al (18), our findings conclusively show that immune surveillance of the small and large intestine is operated by distinct LNs and cells dedicated to these structures. The finding that pDCs upregulated expression of proinflammatory cytokine genes as well as genes involved in pathogen sensing underscores the importance of pDCs in coMLNs as active sentinels of inflammation in the colon.…”

“…RALDH (Aldh1a2) mRNA expression was lower in coMLN-derived CD103 + DCs compared with CD103 + DCs in siMLN, consistent with the findings of Houston et al (18). This finding is in line with the notion that CD103 + DCs in coMLN and siMLN are not identical and that T cells are likely not imprinted with CCR9 expression in coMLN.…”

“…(17), that lymphatics from different parts of the intestine drain into different parts of the cluster of MLN in the mouse. However, only very recently, Houston et al (18) documented for the first time, to our knowledge, the existence of three LNs draining lymph specifically from the colon and showed evidence of CD103 + cDC migration from colon into these LNs. Whereas the standard method to detect lymphatic drainage to a given LN has been to inject ink such as Evan blue into the tissue of interest, we used subserosal injections of FITC-Dx into the colon wall and dissected thereafter the whole gut and mesenterium en bloc for fluorescence microscopy.…”

“…They identified three novel colondraining LNs distinct from the main MLN draining small intestine. The unique phenotypes of their CD103 + DC subsets and T cells and the inability of CD103 + DCs in these LNs to prime T cells in response to small-intestinal and oral Ags indicated that these LNs and their DC segregate from the immune surveillance of the small intestine (18).…”

CD169 identifies an activated CD8+T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

“…2,3,[6][7][8][9] Regional LNs preferentially accommodate naive lymphocytes and allow these cells to efficiently encounter antigenpresenting cells (APCs) that bring in antigens from surrounding tissues. 10,11 Efficient tumor priming in the draining LN can produce antitumor immunity; however, a modulated LN microenvironment can also provide hospitable soil for the seeding and proliferation of tumor cells that lead to metastases. 12,13 CD8 C T cells play an important effector role in orchestrating host antitumor immunity through their capacity to recognize tumor antigens and confer superior immunological protection against tumors.…”