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PI3K in T Cell Adhesion and Trafficking.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Johansen, Kristoffer H 
Golec, Dominic P 
Thomsen, Julie H 
Schwartzberg, Pamela L 

Abstract

PI3K signalling is required for activation, differentiation, and trafficking of T cells. PI3Kδ, the dominant PI3K isoform in T cells, has been extensively characterised using PI3Kδ mutant mouse models and PI3K inhibitors. Furthermore, characterisation of patients with Activated PI3K Delta Syndrome (APDS) and mouse models with hyperactive PI3Kδ have shed light on how increased PI3Kδ activity affects T cell functions. An important function of PI3Kδ is that it acts downstream of TCR stimulation to activate the major T cell integrin, LFA-1, which controls transendothelial migration of T cells as well as their interaction with antigen-presenting cells. PI3Kδ also suppresses the cell surface expression of CD62L and CCR7 which controls the migration of T cells across high endothelial venules in the lymph nodes and S1PR1 which controls lymph node egress. Therefore, PI3Kδ can control both entry and exit of T cells from lymph nodes as well as the recruitment to and retention of T cells within inflamed tissues. This review will focus on the regulation of adhesion receptors by PI3Kδ and how this contributes to T cell trafficking and localisation. These findings are relevant for our understanding of how PI3Kδ inhibitors may affect T cell redistribution and function.

Description

Keywords

CCR7, CD62L, LFA-1, PI3K, adhesion, integrin, trafficking, Animals, Cell Adhesion, Cell Movement, Class I Phosphatidylinositol 3-Kinases, Guanine Nucleotide Exchange Factors, Humans, Immunological Synapses, Integrins, Lymphocyte Function-Associated Antigen-1, Mice, Primary Immunodeficiency Diseases, Signal Transduction, T-Lymphocytes, rho-Associated Kinases

Journal Title

Front Immunol

Conference Name

Journal ISSN

1664-3224
1664-3224

Volume Title

12

Publisher

Frontiers Media SA
Sponsorship
Wellcome Trust (200925/Z/16/Z)