TY - JOUR
T1 - Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease
AU - Randolph, Gwendalyn J.
AU - Bala, Shashi
AU - Rahier, Jean François
AU - Johnson, Michael W.
AU - Wang, Peter L.
AU - Nalbantoglu, I. L.Ke
AU - Dubuquoy, Laurent
AU - Chau, Amélie
AU - Pariente, Benjamin
AU - Kartheuser, Alex
AU - Zinselmeyer, Bernd H.
AU - Colombel, Jean Frederic
N1 - Publisher Copyright:
© 2016 American Society for Investigative Pathology
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Early pathological descriptions of Crohn disease (CD) argued for a potential defect in lymph transport; however, this concept has not been thoroughly investigated. In mice, poor healing in response to infection-induced tissue damage can cause hyperpermeable lymphatic collecting vessels in mesenteric adipose tissue that impair antigen and immune cell access to mesenteric lymph nodes (LNs), which normally sustain appropriate immunity. To investigate whether analogous changes might occur in human intestinal disease, we established a three-dimensional imaging approach to characterize the lymphatic vasculature in mesenteric tissue from controls or patients with CD. In CD specimens, B-cell–rich aggregates resembling tertiary lymphoid organs (TLOs) impinged on lymphatic collecting vessels that enter and exit LNs. In areas of creeping fat, which characterizes inflammation-affected areas of the bowel in CD, we observed B cells and apparent innate lymphoid cells that had invaded the lymphatic vessel wall, suggesting these cells may be mediators of lymphatic remodeling. Although TLOs have been described in many chronic inflammatory states, their anatomical relationship to preestablished LNs has never been revealed. Our data indicate that, at least in the CD-affected mesentery, TLOs are positioned along collecting lymphatic vessels in a manner expected to affect delivery of lymph to LNs.
AB - Early pathological descriptions of Crohn disease (CD) argued for a potential defect in lymph transport; however, this concept has not been thoroughly investigated. In mice, poor healing in response to infection-induced tissue damage can cause hyperpermeable lymphatic collecting vessels in mesenteric adipose tissue that impair antigen and immune cell access to mesenteric lymph nodes (LNs), which normally sustain appropriate immunity. To investigate whether analogous changes might occur in human intestinal disease, we established a three-dimensional imaging approach to characterize the lymphatic vasculature in mesenteric tissue from controls or patients with CD. In CD specimens, B-cell–rich aggregates resembling tertiary lymphoid organs (TLOs) impinged on lymphatic collecting vessels that enter and exit LNs. In areas of creeping fat, which characterizes inflammation-affected areas of the bowel in CD, we observed B cells and apparent innate lymphoid cells that had invaded the lymphatic vessel wall, suggesting these cells may be mediators of lymphatic remodeling. Although TLOs have been described in many chronic inflammatory states, their anatomical relationship to preestablished LNs has never been revealed. Our data indicate that, at least in the CD-affected mesentery, TLOs are positioned along collecting lymphatic vessels in a manner expected to affect delivery of lymph to LNs.
UR - http://www.scopus.com/inward/record.url?scp=84995887416&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2016.07.026
DO - 10.1016/j.ajpath.2016.07.026
M3 - Article
C2 - 27746181
AN - SCOPUS:84995887416
SN - 0002-9440
VL - 186
SP - 3066
EP - 3073
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 12
ER -