Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement
Dendritic cell–T cell (DC-T) contacts play an important role in T cell activation, clone generation, and development. Regulating the cytoskeletal protein rearrangement of DCs can modulate DC-T contact and affect T cell activation. However, inhibitory factors on cytoskeletal regulation in DCs remain...
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2021-01-01
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doaj-6de1e24943a94cbc8071282ace0f9b152021-01-22T06:06:59ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-01-01810.3389/fcell.2020.605713605713Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin RearrangementWei LinShuping ZhouMeng FengYong YuQinghong SuXiaofan LiDendritic cell–T cell (DC-T) contacts play an important role in T cell activation, clone generation, and development. Regulating the cytoskeletal protein rearrangement of DCs can modulate DC-T contact and affect T cell activation. However, inhibitory factors on cytoskeletal regulation in DCs remain poorly known. We showed that a soluble form of CD83 (sCD83) inhibited T cell activation by decreasing DC-T contact and synapse formation between DC and T cells. This negative effect of sCD83 on DCs was mediated by disruption of F-actin rearrangements, leading to alter expression and localization of major histocompatibility complex class II (MHC-II) and immunological synapse formation between DC and T cells. Furthermore, sCD83 was found to decrease GTP-binding activity of Rab1a, which further decreased colocalization and expression of LRRK2 and F-actin rearrangements in DCs, leading to the loss of MHC-II at DC-T synapses and reduced DC-T synapse formation. Further, sCD83-treated DCs alleviated symptoms of experimental autoimmune uveitis in mice and decreased the number of T cells in the eyes and lymph nodes of these animals. Our findings demonstrate a novel signaling pathway of sCD83 on regulating DC-T contact, which may be harnessed to develop new immunosuppressive therapeutics for autoimmune disease.https://www.frontiersin.org/articles/10.3389/fcell.2020.605713/fullsCD83DC-T contactRab1Aimmunological synapseautoimmune uveitis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Lin Shuping Zhou Meng Feng Yong Yu Qinghong Su Xiaofan Li |
spellingShingle |
Wei Lin Shuping Zhou Meng Feng Yong Yu Qinghong Su Xiaofan Li Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement Frontiers in Cell and Developmental Biology sCD83 DC-T contact Rab1A immunological synapse autoimmune uveitis |
author_facet |
Wei Lin Shuping Zhou Meng Feng Yong Yu Qinghong Su Xiaofan Li |
author_sort |
Wei Lin |
title |
Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement |
title_short |
Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement |
title_full |
Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement |
title_fullStr |
Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement |
title_full_unstemmed |
Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement |
title_sort |
soluble cd83 regulates dendritic cell–t cell immunological synapse formation by disrupting rab1a-mediated f-actin rearrangement |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-01-01 |
description |
Dendritic cell–T cell (DC-T) contacts play an important role in T cell activation, clone generation, and development. Regulating the cytoskeletal protein rearrangement of DCs can modulate DC-T contact and affect T cell activation. However, inhibitory factors on cytoskeletal regulation in DCs remain poorly known. We showed that a soluble form of CD83 (sCD83) inhibited T cell activation by decreasing DC-T contact and synapse formation between DC and T cells. This negative effect of sCD83 on DCs was mediated by disruption of F-actin rearrangements, leading to alter expression and localization of major histocompatibility complex class II (MHC-II) and immunological synapse formation between DC and T cells. Furthermore, sCD83 was found to decrease GTP-binding activity of Rab1a, which further decreased colocalization and expression of LRRK2 and F-actin rearrangements in DCs, leading to the loss of MHC-II at DC-T synapses and reduced DC-T synapse formation. Further, sCD83-treated DCs alleviated symptoms of experimental autoimmune uveitis in mice and decreased the number of T cells in the eyes and lymph nodes of these animals. Our findings demonstrate a novel signaling pathway of sCD83 on regulating DC-T contact, which may be harnessed to develop new immunosuppressive therapeutics for autoimmune disease. |
topic |
sCD83 DC-T contact Rab1A immunological synapse autoimmune uveitis |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2020.605713/full |
work_keys_str_mv |
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