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Dendritic cell migration to skin-draining lymph nodes is controlled by dermatan sulfate and determines adaptive immunity magnitude

Nadafi, Reza; Koning, Jasper J.; Veninga, Henrike; Stachtea, Xanthi N. LU ; Konijn, Tanja; Zwiers, Antonie; Malmström, Anders LU ; den Haan, Joke M.M.; Mebius, Reina E. and Maccarana, Marco LU , et al. (2018) In Frontiers in Immunology 9(FEB).
Abstract

For full activation of naïve adaptive lymphocytes in skin-draining lymph nodes (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived dendritic cells (DCs) that encountered antigens (Ags) is an absolute prerequisite. To get to the nearest draining LN upon intradermal immunization, DCs need to migrate from the infection site to the afferent lymphatics, which can only be reached by traversing a collagen-dense network located in the dermis of the skin through the activity of proteolytic enzymes. Here, we show that mice with altered collagen fibrillogenesis resulting in thicker collagen fibers in the skin display a reduced DC migration to the draining LN upon immune challenge. Consequently, the initiation of the... (More)

For full activation of naïve adaptive lymphocytes in skin-draining lymph nodes (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived dendritic cells (DCs) that encountered antigens (Ags) is an absolute prerequisite. To get to the nearest draining LN upon intradermal immunization, DCs need to migrate from the infection site to the afferent lymphatics, which can only be reached by traversing a collagen-dense network located in the dermis of the skin through the activity of proteolytic enzymes. Here, we show that mice with altered collagen fibrillogenesis resulting in thicker collagen fibers in the skin display a reduced DC migration to the draining LN upon immune challenge. Consequently, the initiation of the cellular and humoral immune response was diminished. Ag-specific CD8+ and CD4+ T cells as well as Ag-specific germinal center B cells and serum immunoglobulin levels were significantly decreased. Hence, we postulate that alterations to the production of extracellular matrix, as seen in various connective tissue disorders, may in the end affect the qualitative outcome of adaptive immunity.

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published
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keywords
Adaptive immunity, Antigen, Collagen, Dendritic cells, Dermatan sulfate epimerase, Dse, Ehlers-Danlos syndrome, Skin-draining lymph node
in
Frontiers in Immunology
volume
9
issue
FEB
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85041827016
DOI
10.3389/fimmu.2018.00206
language
English
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yes
id
2e2272eb-3eb0-4776-8f9b-c038cb8f63d7
date added to LUP
2018-03-01 11:10:51
date last changed
2018-06-01 03:00:26
@article{2e2272eb-3eb0-4776-8f9b-c038cb8f63d7,
  abstract     = {<p>For full activation of naïve adaptive lymphocytes in skin-draining lymph nodes (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived dendritic cells (DCs) that encountered antigens (Ags) is an absolute prerequisite. To get to the nearest draining LN upon intradermal immunization, DCs need to migrate from the infection site to the afferent lymphatics, which can only be reached by traversing a collagen-dense network located in the dermis of the skin through the activity of proteolytic enzymes. Here, we show that mice with altered collagen fibrillogenesis resulting in thicker collagen fibers in the skin display a reduced DC migration to the draining LN upon immune challenge. Consequently, the initiation of the cellular and humoral immune response was diminished. Ag-specific CD8+ and CD4+ T cells as well as Ag-specific germinal center B cells and serum immunoglobulin levels were significantly decreased. Hence, we postulate that alterations to the production of extracellular matrix, as seen in various connective tissue disorders, may in the end affect the qualitative outcome of adaptive immunity.</p>},
  articleno    = {206},
  author       = {Nadafi, Reza and Koning, Jasper J. and Veninga, Henrike and Stachtea, Xanthi N. and Konijn, Tanja and Zwiers, Antonie and Malmström, Anders and den Haan, Joke M.M. and Mebius, Reina E. and Maccarana, Marco and Reijmers, Rogier M.},
  keyword      = {Adaptive immunity,Antigen,Collagen,Dendritic cells,Dermatan sulfate epimerase,Dse,Ehlers-Danlos syndrome,Skin-draining lymph node},
  language     = {eng},
  month        = {02},
  number       = {FEB},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Immunology},
  title        = {Dendritic cell migration to skin-draining lymph nodes is controlled by dermatan sulfate and determines adaptive immunity magnitude},
  url          = {http://dx.doi.org/10.3389/fimmu.2018.00206},
  volume       = {9},
  year         = {2018},
}