On the cover
CCL21 and VE-cadherin afferent lymphatic distribution
T cells and dendritic cells (DC) migrate from tissues into draining lymph nodes (dLN) through afferent lymphatics, which are critical for their functions of priming to antigen, anamnestic responses, resolution of inflammation, and regulatory T cell (Treg) suppression. In particular, Treg migration from tissues into lymphatics and dLN is essential for suppressive function to enhance islet allograft survival (1, 2, 3). Shown is a 3-D confocal image of murine ear pinna afferent lymphatics stained for the lymphatic marker lymphatic vessel endothelial hyaluronan receptor 1 (Lyve-1), the homeostatic chemokine CCL21, and the junctional protein vascular endothelial (VE)-cadherin. The image shows CCL21 distribution within lymphatic endothelial cell (LEC) perikarya, which is released upon T cell or DC contact topromote their LN migration. VE-cadherin forms “buttons” and “zippers” between adjacent LEC, determining permeability of junctions for migration of leukocytes from the interstitium into the lymphatic lumen.
Authors: Yanbao Xiong, Wenji Piao, Jonathan S Bromberg
 Zhang N, Schröppel B, Lal G, Jakubzick C, Mao X, Chen D, Yin N, Jessberger R, Ochando JC, Ding Y, Bromberg JS. Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response. Immunity. 2009 Mar 20; 30(3): 458-69.
 Xiong Y, Ahmad S, Iwami D, Brinkman CC, Bromberg JS. T-bet Regulates Natural Regulatory T Cell Afferent Lymphatic Migration and Suppressive Function. J Immunol. 2016 Mar 15; 196(6): 2526-40.
 Brinkman CC, Iwami D, Hritzo MK, Xiong Y, Ahmad S, Simon T, Hippen KL, Blazar BR, Bromberg JS. Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration. Nat Commun. 2016 Jun 21; 7: 12021.