Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Johnson, Louise A, Banerji, Suneale, Lagerholm, B Christoffer, Jackson, David G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2021
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
_version_ 1783672789830467584
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
work_keys_str_mv AT johnsonlouisea dendriticcellentrytolymphaticcapillariesisorchestratedbycd44andthehyaluronanglycocalyx
AT banerjisuneale dendriticcellentrytolymphaticcapillariesisorchestratedbycd44andthehyaluronanglycocalyx
AT lagerholmbchristoffer dendriticcellentrytolymphaticcapillariesisorchestratedbycd44andthehyaluronanglycocalyx
AT jacksondavidg dendriticcellentrytolymphaticcapillariesisorchestratedbycd44andthehyaluronanglycocalyx