@article{c0c61e6e7751435fbfda8b955e103adc,
title = "Induced regulatory T cells superimpose their suppressive capacity with effector T cells in lymph nodes via antigen-specific S1p1-dependent egress blockage",
abstract = "Regulatory T cells (Tregs) restrict overexuberant lymphocyte activation. While close proximity between Tregs and their suppression targets is important for optimal inhibition, and literature indicates that draining lymph nodes (LNs) may serve as a prime location for the suppression, signaling details orchestrating this event are not fully characterized. Using a protocol to enable peripheral generation of inducible antigen-specific Tregs (asTregs) to control allergen-induced asthma, we have identified an antigen-specific mechanism that locks asTregs within hilar LNs which in turn suppresses airway inflammation. The suppressive asTregs, upon antigen stimulation in the LN, downregulate sphingosine-1-phosphate receptor 1 egress receptor expression. These asTregs in turn mediate the downregulation of the same receptor on incoming effector T cells. Therefore, asTregs and effector T cells are locked in these draining LNs for prolonged interactions. Disruption of individual steps of this retention sequence abolishes the inflammation controlled by asTregs. Collectively, this study identifies a new requirement of spatial congregation with their suppression targets essential for asTreg functions and suggests therapeutic programs via Treg traffic control.",
keywords = "Airway inflammation, Antigen specific suppression, Egress, Hilar lymph node, Inducible regulatory T cell, S1p1",
author = "Shuang Geng and Yiwei Zhong and Xiaoyu Zhou and Gan Zhao and Xiaoping Xie and Yechun Pei and Hu Liu and Huiyuan Zhang and Yan Shi and Bin Wang",
note = "Funding Information: We would like to thank Drs. Guoxing Zheng and Bing Sun for his valuable suggestions and critics. We are grateful for Drs. Ying Wan, Dawei Li, Minghui Zhang, Hai Qi, and Zhinan Yin for their kindly sharing their reagents and transgenic animals. We would like to express our gratitude to Drs. Mingzhao Zhu and Yangxin Fu who provided us the LTbIg reagents and technique supports. We would like to thank Dr. Melanie Stenner for proofreading and critical comments. We would also like to thank Dr. Qingling Yu and Mr. Zhonghuai He for their kind supports for this project. This work was supported in part by the Chinese National Natural Science Foundation (30930068, 31430027, and 81672016), High-Tech 863 Program of China (2012AA02A407), and New Drug Discovery Program (2013ZX09102041) to BW. YS is supported by Tsinghua-Peking Center for Life Sciences and grants from US National Institutes of Health (R01AI098995 and R21AI089963), Natural Sciences and Engineering Research Council of Canada (RGPIN-355350/396037), and Canadian Institutes for Health Research (MOP-119295). Publisher Copyright: {\textcopyright} 2017 Geng, Zhong, Zhou, Zhao, Xie,Pei, Liu, Zhang, Shi and Wang.",
year = "2017",
month = jun,
day = "7",
doi = "10.3389/fimmu.2017.00663",
language = "English (US)",
volume = "8",
journal = "Frontiers in immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "JUN",
}