Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage
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 detail...
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doaj-8a3fd436e97643198a052125e476dab72020-11-24T22:40:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-06-01810.3389/fimmu.2017.00663261134Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress BlockageShuang Geng0Yiwei Zhong1Xiaoyu Zhou2Gan Zhao3Xiaoping Xie4Yechun Pei5Hu Liu6Huiyuan Zhang7Yan Shi8Yan Shi9Bin Wang10Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, ChinaKey Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, ChinaKey Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, ChinaKey Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, ChinaState Key Laboratory for Agro-Biotechnology, China Agricultural University, Beijing, ChinaState Key Laboratory for Agro-Biotechnology, China Agricultural University, Beijing, ChinaState Key Laboratory for Agro-Biotechnology, China Agricultural University, Beijing, ChinaState Key Laboratory for Agro-Biotechnology, China Agricultural University, Beijing, ChinaTsinghua-Peking Center for Life Sciences; Institute for Immunology, School of Medicine, Tsinghua University, Beijing, ChinaDepartment of Microbiology, Immunology and Infectious Diseases, Snyder Institute, University of Calgary, Calgary, AB, CanadaKey Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, ChinaRegulatory 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00663/fullinducible regulatory T cellantigen specific suppressionhilar lymph nodeairway inflammationegressS1p1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuang Geng Yiwei Zhong Xiaoyu Zhou Gan Zhao Xiaoping Xie Yechun Pei Hu Liu Huiyuan Zhang Yan Shi Yan Shi Bin Wang |
spellingShingle |
Shuang Geng Yiwei Zhong Xiaoyu Zhou Gan Zhao Xiaoping Xie Yechun Pei Hu Liu Huiyuan Zhang Yan Shi Yan Shi Bin Wang Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage Frontiers in Immunology inducible regulatory T cell antigen specific suppression hilar lymph node airway inflammation egress S1p1 |
author_facet |
Shuang Geng Yiwei Zhong Xiaoyu Zhou Gan Zhao Xiaoping Xie Yechun Pei Hu Liu Huiyuan Zhang Yan Shi Yan Shi Bin Wang |
author_sort |
Shuang Geng |
title |
Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage |
title_short |
Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage |
title_full |
Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage |
title_fullStr |
Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage |
title_full_unstemmed |
Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage |
title_sort |
induced regulatory t cells superimpose their suppressive capacity with effector t cells in lymph nodes via antigen-specific s1p1-dependent egress blockage |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-06-01 |
description |
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. |
topic |
inducible regulatory T cell antigen specific suppression hilar lymph node airway inflammation egress S1p1 |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00663/full |
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