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.
View: Text | PDF
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

×

Figure 3

LECs can suppress immunity and promote tolerance in multiple ways.

Options: View larger image (or click on image) Download as PowerPoint
LECs can suppress immunity and promote tolerance in multiple ways. (A) L...
(A) LECs interact with DCs via binding of ICAM-1 to Mac-1, inhibiting DC maturation and thus dampening their ability to effectively activate T cells. (B) LECs that have been activated by T cell–derived pro-inflammatory cytokines can inhibit T cell proliferation through the production of molecules such as IDO, TGF-β, and NO, which suppress T cell activation. (C) LECs can directly present endogenous PTAs and cross-present exogenous antigens to naive CD8+ T cells to induce dysfunctional T cell activation and tolerance due to expression of the inhibitory receptor PD-L1 and lack of co-stimulatory molecules on the surface of LECs.