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Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx
DCs play a vital role in immunity by conveying antigens from peripheral tissues to draining lymph nodes, through afferent lymphatic vessels. Critical to the process is initial docking to the lymphatic endothelial receptor LYVE-1 via its ligand hyaluronan on the DC surface. How this relatively weak b...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008951/ https://www.ncbi.nlm.nih.gov/pubmed/33687996 http://dx.doi.org/10.26508/lsa.202000908 |
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author | Johnson, Louise A Banerji, Suneale Lagerholm, B Christoffer Jackson, David G |
author_facet | Johnson, Louise A Banerji, Suneale Lagerholm, B Christoffer Jackson, David G |
author_sort | Johnson, Louise A |
collection | PubMed |
description | DCs play a vital role in immunity by conveying antigens from peripheral tissues to draining lymph nodes, through afferent lymphatic vessels. Critical to the process is initial docking to the lymphatic endothelial receptor LYVE-1 via its ligand hyaluronan on the DC surface. How this relatively weak binding polymer is configured for specific adhesion to LYVE-1, however, is unknown. Here, we show that hyaluronan is anchored and spatially organized into a 400–500 nm dense glycocalyx by the leukocyte receptor CD44. Using gene knockout and by modulating CD44-hyaluronan interactions with monoclonal antibodies in vitro and in a mouse model of oxazolone-induced skin inflammation, we demonstrate that CD44 is required for DC adhesion and transmigration across lymphatic endothelium. In addition, we present evidence that CD44 can dynamically control the density of the hyaluronan glycocalyx, regulating the efficiency of DC trafficking to lymph nodes. Our findings define a previously unrecognized role for CD44 in lymphatic trafficking and highlight the importance of the CD44:HA:LYVE-1 axis in its regulation. |
format | Online Article Text |
id | pubmed-8008951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-80089512021-04-02 Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx Johnson, Louise A Banerji, Suneale Lagerholm, B Christoffer Jackson, David G Life Sci Alliance Research Articles DCs play a vital role in immunity by conveying antigens from peripheral tissues to draining lymph nodes, through afferent lymphatic vessels. Critical to the process is initial docking to the lymphatic endothelial receptor LYVE-1 via its ligand hyaluronan on the DC surface. How this relatively weak binding polymer is configured for specific adhesion to LYVE-1, however, is unknown. Here, we show that hyaluronan is anchored and spatially organized into a 400–500 nm dense glycocalyx by the leukocyte receptor CD44. Using gene knockout and by modulating CD44-hyaluronan interactions with monoclonal antibodies in vitro and in a mouse model of oxazolone-induced skin inflammation, we demonstrate that CD44 is required for DC adhesion and transmigration across lymphatic endothelium. In addition, we present evidence that CD44 can dynamically control the density of the hyaluronan glycocalyx, regulating the efficiency of DC trafficking to lymph nodes. Our findings define a previously unrecognized role for CD44 in lymphatic trafficking and highlight the importance of the CD44:HA:LYVE-1 axis in its regulation. Life Science Alliance LLC 2021-03-09 /pmc/articles/PMC8008951/ /pubmed/33687996 http://dx.doi.org/10.26508/lsa.202000908 Text en © 2021 Johnson et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Johnson, Louise A Banerji, Suneale Lagerholm, B Christoffer Jackson, David G Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx |
title | Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx |
title_full | Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx |
title_fullStr | Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx |
title_full_unstemmed | Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx |
title_short | Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx |
title_sort | dendritic cell entry to lymphatic capillaries is orchestrated by cd44 and the hyaluronan glycocalyx |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008951/ https://www.ncbi.nlm.nih.gov/pubmed/33687996 http://dx.doi.org/10.26508/lsa.202000908 |
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