Where is the mesenteric lymph nodes located

DCs continually migrate from intestinal tissues to the MLNs where they present antigen and control the development, migration, and functional differentiation of cells of the adaptive immune system. The MLN is often assumed to be the LN draining both the SI and colon, despite the fact that studies have shown different parts of the intestine drain to distinct nodes in the MLN chain.

The anatomy of lymphatic drainage from the SI and colon was first examined over 40 years ago 11 , 12 and a more recent study has updated these findings.

As the SI and colon are immunologically distinct and drain to different regions of the MLNs, we hypothesized that the different nodes of the MLNs would reflect the characteristics of the different environments that influence them. We predicted therefore that migratory cells, and in particular DCs, found in the distinct mesenteric nodes, and the nodes themselves, would display different functions.

There are many features of intestinal DCs that may differ between the SI and colon, and therefore between different nodes within the mesenteric chain. Despite this, many groups, including ourselves, have previously failed to discriminate between the distinct MLN nodes when examining the populations of cells migrating from both the SI and colon.

Here we confirm that lymph drains from different regions of the intestine to different nodes within the MLNs, and describe the anatomically distinct migration pathways of DCs from the SI and colon.

In addition, we show that DCs originating from the SI induce T-cell responses in specific nodes of the MLN, and that different nodes contain T cells with distinct characteristics. Our data emphasize the immunological separation of responses originating in the SI and colon, and have far-reaching implications, both for those performing analyses of intestinal immune responses and for those developing tissue-specific treatments for pathologies that affect specific regions of the intestine.

To identify the individual nodes draining each part of the intestine we visualized and compared the lymphatic drainage from the SI and colon. To achieve this, Evans blue dye was injected beneath the subserosal layer into the intestinal wall.

The dye was carried from the tissue by the afferent lymphatics, allowing direct examination of the lymphatic system and identification of the specific nodes draining the injected area Figure 1a—e.

Following injection of Evans blue into the SI, the central mesenteric nodes stained blue Figure 1b. When Evans blue was injected into the proximal colon, the dye reached the first node in the MLN chain, located closest to the cecum Figure 1c. Interestingly, a second node also stained blue following injection of dye into the proximal colon. This LN was inferior to the main MLN chain, close to the abdominal aorta, and distal to the superior mesenteric vein Figure 1d.

Following Evans blue injection into the distal colon, the first mesenteric node to stain blue was located in the intestinal mesentery adjacent to the abdominal aorta Figure 1e. This is likely to be the inferior mesenteric node. Collectively, these three nodes that drain the lymph from the colon will be referred to as the colonic MLN cMLN ; a diagram highlighting their positioning and a schematic representing the lymphatic drainage to the sMLN and cMLN are shown in Figure 1f—h.

The iliac LNs are located adjacent to the spine, anterior of the aortic bifurcation, and were not labeled with Evans blue after any of our injections. They may drain lymph from the caudal nodes, which drain the rectum.

The intestines were exposed at laparotomy a , and Evans blue dye was injected underneath the serosa of either the SI b , the proximal colon c , d or distal colon e , or were uninjected a , f.

Five minutes later, MLNs were photographed. The iliac and caudal nodes, located against the spine, adjacent to the aortic bifurcation, are represented in grey h.

The numbers of photoconverted migratory dendritic cells DCs were analyzed. Each dot represents an individual replicate and are pooled from at least two independent experiments. PowerPoint slide. To identify how the separation of the lymphatic drainage from the SI and colon influenced the destinations of the DCs migrating from the intestine, we used transgenic mice that ubiquitously express the green fluorescent Kaede protein.

This protein is irreversibly converted from green to red fluorescence following exposure to low-intensity violet light. Thus, detectable photoconversion occurs in a high frequency of target cells and is restricted to the site of light exposure. In some experiments, violet light exposure was confined to smaller regions of the SI or colon, revealing that photoconversion of specific regions of the SI or colon reproducibly results in significant enrichment of Kaede-red DCs in individual nodes of the sMLN or cMLN Figure 2.

Immediately afterwards, single-cell suspensions were prepared from the intestinal tissues of two mice, to confirm the photoconversion procedures had been successful a. The proportions of photoconverted migratory DCs were analyzed. Each dot represents an individual animal. We and others have observed striking differences between the DC populations in the mucosa of the SI and colon. This might reflect a downregulation of CD expression on arrival in the LN. Data are presented as means and are pooled from two independent experiments.

Our previous studies have also shown that DCs migrating in pseudo-afferent lymph express low levels of the eosinophil marker SiglecF. To examine the functional consequences of the anatomical compartmentalization of DC migration from the SI and colon, we investigated whether antigen acquired in the SI was preferentially presented by DCs in the sMLN. We observed this to be true at all ratios of DCs to T cells, from down to data not shown. The graph shows data from four mice. The graph shows data from 11 mice, from 2 independent experiments.

Recent work has indicated that GPR15 has a role in leukocyte homing to the colon. To investigate these Tregs more closely, we examined expression of neuropilin-1, to distinguish natural from induced Tregs. ST-2 has recently been reported to be preferentially expressed on colonic Tregs.

Histograms show representative examples of staining from each tissue. Dot plots show representative data. Graphs show analysis of results from 14 mice, pooled from 2 independent experiments. These data indicate that colonic DCs may not be influenced by the immunomodulatory effects of dietary agents such as vitamin A. The SI and colon represent vastly different immunological niches; therefore, the cells that migrate from the SI or colon are likely to have been exposed to enormously different stimuli.

As DCs are essential for the induction of an adaptive immune response, acting as a bridge between the innate and adaptive immune system we compared lymphatic drainage from the SI and colon, and its effects on DC migration. Here we demonstrate that in the steady state there is anatomical segregation of cell migration between the SI and colon to specific regions of the MLNs. These distinct parts of the MLNs can be examined separately, to allow better analysis of the immune responses in the SI and colon.

To more accurately identify which parts of the intestine supply lymph to each of the nodes of the MLN chain, we examined the lymphatic drainage from the SI and colon by the injection of Evans blue dye. This allowed direct examination of the intestinal afferent lymphatic system and the MLNs that drain the intestine. This phenomenon has previously been observed, with the identification of the middle MLNs draining the jejunum and ileum.

This was consistent with previous reports in mice and rats. Interestingly, a second, previously unreported, node at the opposite end of the MLN chain was also found to be draining the colon. In addition, as previously reported, following the labeling of the distal colon, an LN distinct from the main MLN chain located in the intestinal mesentery adjacent to the abdominal aorta was found to drain the most distal colon.

Therefore, we explored the anatomical segregation of lymphatic drainage from the SI and colon in the steady state using Kaede mice. Kaede mice have previously been used to monitor DC migration in peripheral LNs, 16 as well as B-cell migration in the intestine. To analyze the migration of intestinal DCs, mice underwent the photoconversion of either the SI or colon, and the migration of photoconverted Kaede-red DCs was compared.

The characteristics of the DCs in the colon have been less well documented. We analyzed the functional consequences of the anatomical segregation of migrating intestinal DCs by examining whether antigens acquired in SI were presented only in the sMLN.

Although the exact mechanisms controlling uptake of soluble antigen are unclear, DCs in the LP are able to acquire soluble antigen. As predicted, T-cell proliferation was only detected in the sMLN. Therefore, there is not only anatomical segregation of the lymphatic drainage from the SI and colon in the steady state, but the sMLN and cMLN are also functionally separate; antigen expressed in the SI causes proliferation of naive T cells in the sMLNs. Therefore, under most circumstances, it is beneficial to analyze immune responses in these distinct MLNs separately.

The mechanism by which GPR15 mediates colon homing of T cells is therefore not clear. Understanding how T cells home to the colon is a matter of immunological importance and deserves further investigation. These data may indicate that colonic DCs are influenced less by the immunomodulatory effects of dietary agents and are therefore functionally fundamentally different to SI DCs. These basic differences between DCs from the SI and colon are likely to reflect the necessary anatomical compartmentalization of the immune response required between the SI and colon.

DCs from the SI and colon are influenced by different factors. Although DCs from the SI are influenced by dietary agents, its likely that colonic DCs located adjacent to the major microbial burden are more likely to be influenced by microbial agents.

This disassociation of the immune response between the SI and colon is likely to be beneficial, enabling responding T cells to be directed to the most appropriate intestinal compartment. Show references Hay WW, et al. Viral infections. New York, N. Accessed June 18, Nauman MI.

Causes of acute abdominal pain in children and adolescents. Helbling R, et al. Acute nonspecific mesenteric lymphadenitis: More than "no need for surgery. Benetti C, et al. Course of acute nonspecific mesenteric lymphadenitis: Single-center experience. European Journal of Pediatrics. Ferri FF. Mesenteric adenitis. In: Ferri's Clinical Advisor Philadelphia, Pa. Many of these causes may also result in lymphadenopathy elsewhere in the body. It is important to recognize mesenteric lymphadenopathy in patients with a history of a primary carcinoma because the lymphadenopathy affects the staging of the disease, which in turn will affect further management.

In addition, mesenteric lymphadenopathy may be the only indicator of an underlying inflammatory or infectious process causing abdominal pain. The distribution of the lymph nodes may indicate the exact nature of the underlying disease process, and the correct treatment may then be instituted.