Bibliographic Details
| Title: |
Efficient T Cell Migration and Activation Require L-Plastin |
| Authors: |
Hemant Joshi, Sharon Celeste Morley |
| Source: |
Frontiers in Immunology, Vol 13 (2022) |
| Publisher Information: |
Frontiers Media S.A., 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
T cells, L-plastin, immune synapse formation, immune cell adhesion and migration, mechanotransduction, LFA-1 (CD11A/CD18, ITGAL/ITGB2), Immunologic diseases. Allergy, RC581-607 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2022.916137/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2022.916137 |
| Access URL: |
https://doaj.org/article/eb0398f4b7fc4b69a280b3ef53ef1664 |
| Accession Number: |
edsdoj.b0398f4b7fc4b69a280b3ef53ef1664 |
| Database: |
Directory of Open Access Journals |
