Emerging roles of lymphatic endothelium in regulating adaptive immunity
Catherine M. Card, … , Shann S. Yu, Melody A. Swartz
Catherine M. Card, … , Shann S. Yu, Melody A. Swartz
Published March 3, 2014
Citation Information: J Clin Invest. 2014;124(3):943-952. https://doi.org/10.1172/JCI73316.
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Review Series

Emerging roles of lymphatic endothelium in regulating adaptive immunity

Abstract

Emerging research on the roles of stromal cells in modulating adaptive immune responses has included a new focus on lymphatic endothelial cells (LECs). LECs are presumably the first cells that come into direct contact with peripheral antigens, cytokines, danger signals, and immune cells travelling from peripheral tissues to lymph nodes. LECs can modulate dendritic cell function, present antigens to T cells on MHC class I and MHC class II molecules, and express immunomodulatory cytokines and receptors, which suggests that their roles in adaptive immunity are far more extensive than previously realized. This Review summarizes the emergent evidence that LECs are important in maintaining peripheral tolerance, limiting and resolving effector T cell responses, and modulating leukocyte function.

Authors

Catherine M. Card, Shann S. Yu, Melody A. Swartz

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Figure 1

Lymphatic vessels continuously provide local information about the tissues they drain to various cells in the LNs.

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Lymphatic vessels continuously provide local information about the tissu...
Lymph-borne antigens may be foreign or self-antigens derived from physiologic cellular metabolism, tissue destruction, and apoptotic cells. Left: immunostained section of a mouse LN shows B cell follicles (B220, green), T cells (CD3e, red), and lymphatic vessels (LYVE-1, white). Right: schematic of the subcapsular sinus, where soluble antigens can access the T cell zone via small conduits enwrapped by FRCs or be taken up by subcapsular macrophages (SCMs). DCs also enter via afferent lymphatic vessels and are attracted by the chemokines CCL19 and CCL21, which bind their receptor CCR7 and which are produced by FRCs and lymphatic endothelium. Naive and regulatory T cells, which also express CCR7, enter mostly through HEVs and less frequently through afferent lymphatics. In the B cell zone, conduits lined by follicular dendritic cells (not shown) enable B cells to rapidly access small antigens that enter from the subcapsular sinus.