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Front Immunol. 2018 Nov 20;9:2655. doi: 10.3389/fimmu.2018.02655. eCollection 2018.

Phosphatase of Regenerating Liver-1 (PRL-1) Regulates Actin Dynamics During Immunological Synapse Assembly and T Cell Effector Function.

Author information

1
Department of Immunology, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
2
12 de Octubre Health Research Institute (imas12), Madrid, Spain.
3
Servicio de Inmunología. Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
4
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
5
Department of Cell Biology and Immunology, Center for Molecular Biology Severo Ochoa (CBM-SO), Mayor Council of Scientific Research (CSIC), Madrid, Spain.
6
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.

Abstract

The regulatory role of most dual specific phosphatases during T cell activation remains unknown. Here, we have studied the expression and function of phosphatases of regenerating liver (PRLs: PRL-1, PRL-2, and PRL-3) during T cell activation, as well as, the dynamic delivery of PRL-1 to the Immunological Synapse (IS). We found that T cell activation downregulates the expression of PRL-2, resulting in an increased PRL-1/PRL-2 ratio. PRL-1 redistributed at the IS in two stages: Initially, it was transiently accumulated at scanning membranes enriched in CD3 and actin, and at later times, it was delivered at the contact site from pericentriolar, CD3ζ-containing, vesicles. Once at the established IS, PRL-1 distributed to LFA-1 and CD3ε sites. Remarkably, PRL-1 was found to regulate actin dynamics during IS assembly and the secretion of IL-2. Moreover, pharmacological inhibition of the catalytic activity of the three PRLs reduced the secretion of IL-2. These results provide evidence indicating a regulatory role of PRL-1 during IS assembly and highlight the involvement of PRLs in immune responses by mature T cells.

KEYWORDS:

IL-2; T cell immune response; actin cytoskeleton; immunological synapse; phosphatases of regenerating liver

PMID:
30515156
PMCID:
PMC6255827
DOI:
10.3389/fimmu.2018.02655
[Indexed for MEDLINE]
Free PMC Article

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