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J Exp Med. 2017 Feb;214(2):327-338. doi: 10.1084/jem.20160620. Epub 2017 Jan 12.

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

Author information

1
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 10084, China.
2
Institute for Immunology, School of Medicine, Tsinghua University, Beijing 10084, China.
3
Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, T2N 1N4 Alberta, Canada.
4
Snyder Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
5
Department of Cell Biology and, Cumming School of Medicine, University of Calgary, Calgary, T2N 1N4 Alberta, Canada.
6
Department of Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
7
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 10084, China yanshi@biomed.tsinghua.edu.cn.

Abstract

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner.

PMID:
28082358
PMCID:
PMC5294852
DOI:
10.1084/jem.20160620
[Indexed for MEDLINE]
Free PMC Article

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