PI3K in T Cell Adhesion and Trafficking

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 (...

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Bibliographic Details
Published in:Frontiers in immunology 2021-08, Vol.12, p.708908-708908
Main Authors: Johansen, Kristoffer H, Golec, Dominic P, Thomsen, Julie H, Schwartzberg, Pamela L, Okkenhaug, Klaus
Format: Article
Language:English
Subjects:
adhesion
Animals
CCR7
CD62L
Cell Adhesion
Cell Movement
Class I Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Class I Phosphatidylinositol 3-Kinases - physiology
Guanine Nucleotide Exchange Factors - physiology
Humans
Immunological Synapses - physiology
Immunology
integrin
Integrins - physiology
LFA-1
Lymphocyte Function-Associated Antigen-1 - physiology
Mice
PI3K
Primary Immunodeficiency Diseases - etiology
rho-Associated Kinases - physiology
Signal Transduction - physiology
T-Lymphocytes - physiology
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Summary: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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.708908