Efficient T Cell Migration and Activation Require L-Plastin
Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-ce...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.916137/full |
| _version_ | 1818255509863530496 |
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| author | Hemant Joshi Hemant Joshi Sharon Celeste Morley Sharon Celeste Morley |
| author_facet | Hemant Joshi Hemant Joshi Sharon Celeste Morley Sharon Celeste Morley |
| author_sort | Hemant Joshi |
| collection | DOAJ |
| description | Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T cells. LPL- deficient T cells migrate slowly in response to chemo-attractants such as CXCL12, CCL19, and poorly polarize towards ICAM-1. Loss of LPL impairs thymic egress and intranodal motility. LPL is also required for T-cell IS maturation with APCs, and therefore for efficient cytokine production and proliferation. LPL-/- mice are less susceptible to T-cell mediated pathologies, such as allograft rejection and experimental autoimmune encephalomyelitis (EAE). LPL activity is regulated by its N-terminal “headpiece”, which contains serine and threonine phosphorylation and calcium- and calmodulin-binding sites. LPL phosphorylation is required for lamellipodia formation during adhesion and migration, and also for LFA-1 clustering during IS formation. However, the precise molecular interactions by which LPL supports T-cell functional responses remain unclear. Future studies elucidating LPL-mediated regulation of T-cell migration and/or activation may illuminate pathways for therapeutic targeting in T-cell-mediated diseases. |
| first_indexed | 2024-12-12T17:13:00Z |
| format | Article |
| id | doaj.art-eb0398f4b7fc4b69a280b3ef53ef1664 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T17:13:00Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-eb0398f4b7fc4b69a280b3ef53ef16642022-12-22T00:17:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.916137916137Efficient T Cell Migration and Activation Require L-PlastinHemant Joshi0Hemant Joshi1Sharon Celeste Morley2Sharon Celeste Morley3Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United StatesDivision of Immunobiology, Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, MO, United StatesDivision of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United StatesDivision of Immunobiology, Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, MO, United StatesRapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T cells. LPL- deficient T cells migrate slowly in response to chemo-attractants such as CXCL12, CCL19, and poorly polarize towards ICAM-1. Loss of LPL impairs thymic egress and intranodal motility. LPL is also required for T-cell IS maturation with APCs, and therefore for efficient cytokine production and proliferation. LPL-/- mice are less susceptible to T-cell mediated pathologies, such as allograft rejection and experimental autoimmune encephalomyelitis (EAE). LPL activity is regulated by its N-terminal “headpiece”, which contains serine and threonine phosphorylation and calcium- and calmodulin-binding sites. LPL phosphorylation is required for lamellipodia formation during adhesion and migration, and also for LFA-1 clustering during IS formation. However, the precise molecular interactions by which LPL supports T-cell functional responses remain unclear. Future studies elucidating LPL-mediated regulation of T-cell migration and/or activation may illuminate pathways for therapeutic targeting in T-cell-mediated diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2022.916137/fullT cellsL-plastinimmune synapse formationimmune cell adhesion and migrationmechanotransductionLFA-1 (CD11A/CD18; ITGAL/ITGB2) |
| spellingShingle | Hemant Joshi Hemant Joshi Sharon Celeste Morley Sharon Celeste Morley Efficient T Cell Migration and Activation Require L-Plastin Frontiers in Immunology T cells L-plastin immune synapse formation immune cell adhesion and migration mechanotransduction LFA-1 (CD11A/CD18; ITGAL/ITGB2) |
| title | Efficient T Cell Migration and Activation Require L-Plastin |
| title_full | Efficient T Cell Migration and Activation Require L-Plastin |
| title_fullStr | Efficient T Cell Migration and Activation Require L-Plastin |
| title_full_unstemmed | Efficient T Cell Migration and Activation Require L-Plastin |
| title_short | Efficient T Cell Migration and Activation Require L-Plastin |
| title_sort | efficient t cell migration and activation require l plastin |
| topic | T cells L-plastin immune synapse formation immune cell adhesion and migration mechanotransduction LFA-1 (CD11A/CD18; ITGAL/ITGB2) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.916137/full |
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