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PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity
Although the function of the extracellular region of programmed death ligand 1 (PD-L1) through its interactions with PD-1 on T cells is well studied, little is understood regarding the intracellular domain of PD-L1. Here, we outline a major role for PD-L1 intracellular signaling in the control of de...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688291/ https://www.ncbi.nlm.nih.gov/pubmed/33053342 http://dx.doi.org/10.1016/j.celrep.2020.108258 |
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author | Lucas, Erin D. Schafer, Johnathon B. Matsuda, Jennifer Kraus, Madison Burchill, Matthew A. Tamburini, Beth A. Jirón |
author_facet | Lucas, Erin D. Schafer, Johnathon B. Matsuda, Jennifer Kraus, Madison Burchill, Matthew A. Tamburini, Beth A. Jirón |
author_sort | Lucas, Erin D. |
collection | PubMed |
description | Although the function of the extracellular region of programmed death ligand 1 (PD-L1) through its interactions with PD-1 on T cells is well studied, little is understood regarding the intracellular domain of PD-L1. Here, we outline a major role for PD-L1 intracellular signaling in the control of dendritic cell (DC) migration from the skin to the draining lymph node (dLN). Using a mutant mouse model, we identify a TSS signaling motif within the intracellular domain of PD-L1. The TSS motif proves critical for chemokine-mediated DC migration to the dLN during inflammation. This loss of DC migration, in the PD-L1 TSS mutant, leads to a significant decline in T cell priming when DC trafficking is required for antigen delivery to the dLN. Finally, the TSS motif is required for chemokine receptor signaling downstream of the Gα subunit of the heterotrimeric G protein complex, ERK phosphorylation, and actin polymerization in DCs. |
format | Online Article Text |
id | pubmed-7688291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-76882912020-11-25 PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity Lucas, Erin D. Schafer, Johnathon B. Matsuda, Jennifer Kraus, Madison Burchill, Matthew A. Tamburini, Beth A. Jirón Cell Rep Article Although the function of the extracellular region of programmed death ligand 1 (PD-L1) through its interactions with PD-1 on T cells is well studied, little is understood regarding the intracellular domain of PD-L1. Here, we outline a major role for PD-L1 intracellular signaling in the control of dendritic cell (DC) migration from the skin to the draining lymph node (dLN). Using a mutant mouse model, we identify a TSS signaling motif within the intracellular domain of PD-L1. The TSS motif proves critical for chemokine-mediated DC migration to the dLN during inflammation. This loss of DC migration, in the PD-L1 TSS mutant, leads to a significant decline in T cell priming when DC trafficking is required for antigen delivery to the dLN. Finally, the TSS motif is required for chemokine receptor signaling downstream of the Gα subunit of the heterotrimeric G protein complex, ERK phosphorylation, and actin polymerization in DCs. 2020-10-13 /pmc/articles/PMC7688291/ /pubmed/33053342 http://dx.doi.org/10.1016/j.celrep.2020.108258 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Lucas, Erin D. Schafer, Johnathon B. Matsuda, Jennifer Kraus, Madison Burchill, Matthew A. Tamburini, Beth A. Jirón PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity |
title | PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity |
title_full | PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity |
title_fullStr | PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity |
title_full_unstemmed | PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity |
title_short | PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity |
title_sort | pd-l1 reverse signaling in dermal dendritic cells promotes dendritic cell migration required for skin immunity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688291/ https://www.ncbi.nlm.nih.gov/pubmed/33053342 http://dx.doi.org/10.1016/j.celrep.2020.108258 |
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