Is defective lymphatic drainage a trigger for lymphoid neogenesis?

Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease

“…17 This fits well with evidence and discussion in CD that lymph drainage is impaired. 4,14,18 TLO formation as a feature of CD has been discussed previously.…”

“…19 However, because of the techniques applied herein and the fact that we have extended our analysis into the tissuedthe mesenteric adipose tissuedthat houses collecting lymphatic vessels, we have, for the first time, been able to associate TLOs with collecting lymphatic vessels, which are the major lymphatic vessels that normally supply LNs. Thus, our findings suggest that TLOs, at least in CD but perhaps much more widely, are anatomically located so as not only to take over immunological roles when lymph flow is poor, 17 but to physically participate in altering the course of immunological communication with the draining LN. In contrast to lymphatic capillaries, which readily expand during lymphangiogenesis associated with inflammation, collecting vessels are not known to expand.…”

“…Thus, processes that remodel these vessels may greatly affect communication between LNs and the tissue, such as the intestinal lamina propria, that they normally drain. Even if TLOs perform some of the immunological functions performed by LNs, 17 the types of responses that are coordinated in the two structures may not be fully overlapping. It is furthermore possible that the structural alterations we describe herein to human collecting lymphatic vessels render them obstructed or permeable in a manner similar to the outcomes described in mice infected by Y. pseudotuberculosis 2 or dogs that have been treated to have elevated output pressures in LNs.…”

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

“…Furthermore, they may accumulate antigen and APCs, bypassing the LN and therefore restricting normal LN function [62,101]. Such circumvention of the normal LN may prevent the induction of an appropriate immune response to foreign antigen or, since the LN has important tolerance-maintaining functions described earlier, result in autoimmunity (Fig.…”

“…B cell germinal centers within TLOs are largely responsible for autoantibody production and autoimmunity in chronic inflammation and graft rejection. Additionally, it has been suggested that TLO-associated lymphatic vessels reroute lymph flow from the draining lymph node [101], whereas the enhanced flow that results from lymphangiogenesis in the tumor environment may promote constant soluble antigen presentation that may be a requirement for tolerance maintenance by the draining lymph node. The tolerance-maintaining functions of the draining LN are thereby critically linked to the functionality of peripheral lymphatics, the pattern of drainage and inflammatory state of the tissue lymphatic vessels [1,115].…”