AUTHOR=Geng Shuang , Zhong Yiwei , Zhou Xiaoyu , Zhao Gan , Xie Xiaoping , Pei Yechun , Liu Hu , Zhang Huiyuan , Shi Yan , Wang Bin 

TITLE=Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00663

DOI=10.3389/fimmu.2017.00663

ISSN=1664-3224

ABSTRACT=Regulatory T cells (Tregs) restrict over-exuberant lymphocyte activation.  While close proximity between Tregs and their suppression targets is important for optimal inhibition, and literature indicates that draining lymph nodes 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 lymph node, downregulate S1p1 (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 lymph nodes 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.