Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan Sulfate and Determines Adaptive Immunity Magnitude

Reza Nadafi, Jasper J Koning, Henrike Veninga, Xanthi N Stachtea, Tanja Konijn, Antonie Zwiers, Anders Malmström, Joke M M den Haan, Reina E Mebius, Marco Maccarana, Rogier M Reijmers

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Pages (from-to)206
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - 2018

Cite this

Nadafi, Reza ; Koning, Jasper J ; Veninga, Henrike ; Stachtea, Xanthi N ; Konijn, Tanja ; Zwiers, Antonie ; Malmström, Anders ; den Haan, Joke M M ; Mebius, Reina E ; Maccarana, Marco ; Reijmers, Rogier M. / Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan Sulfate and Determines Adaptive Immunity Magnitude. In: Frontiers in Immunology. 2018 ; Vol. 9. pp. 206.
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title = "Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan Sulfate and Determines Adaptive Immunity Magnitude",
abstract = "For full activation of na{\"i}ve 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.",
author = "Reza Nadafi and Koning, {Jasper J} and Henrike Veninga and Stachtea, {Xanthi N} and Tanja Konijn and Antonie Zwiers and Anders Malmstr{\"o}m and {den Haan}, {Joke M M} and Mebius, {Reina E} and Marco Maccarana and Reijmers, {Rogier M}",
year = "2018",
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language = "English",
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journal = "Frontiers in Immunology: Molecular Innate Immunity",
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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; Konijn, Tanja; Zwiers, Antonie; Malmström, Anders; den Haan, Joke M M; Mebius, Reina E; Maccarana, Marco; Reijmers, Rogier M.

In: Frontiers in Immunology, Vol. 9, 2018, p. 206.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan Sulfate and Determines Adaptive Immunity Magnitude

AU - Nadafi, Reza

AU - Koning, Jasper J

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AU - Stachtea, Xanthi N

AU - Konijn, Tanja

AU - Zwiers, Antonie

AU - Malmström, Anders

AU - den Haan, Joke M M

AU - Mebius, Reina E

AU - Maccarana, Marco

AU - Reijmers, Rogier M

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AB - 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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