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

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.

Koning, Jasper J.Amsterdam UMC - Vrije Universiteit Amsterdam (author)
Veninga, HenrikeAmsterdam UMC - Vrije Universiteit Amsterdam (author)
Stachtea, Xanthi N.Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)med-xis (author)
Konijn, TanjaAmsterdam UMC - Vrije Universiteit Amsterdam (author)
Zwiers, AntonieAmsterdam UMC - Vrije Universiteit Amsterdam (author)
Malmström, AndersLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)medk-ama (author)
den Haan, Joke M.M.Amsterdam UMC - Vrije Universiteit Amsterdam (author)
Mebius, Reina E.Amsterdam UMC - Vrije Universiteit Amsterdam (author)
Maccarana, MarcoLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)medk-mm0 (author)
Reijmers, Rogier M.Amsterdam UMC - Vrije Universiteit Amsterdam (author)
Amsterdam UMC - Vrije Universiteit AmsterdamInstitutionen för experimentell medicinsk vetenskap (creator_code:org_t)

By the author/editor: Nadafi, Reza; Koning, Jasper J ...; Veninga, Henrike; Stachtea, Xanthi ...; Konijn, Tanja; Zwiers, Antonie; show more...; Malmström, Ander ...; den Haan, Joke M ...; Mebius, Reina E.; Maccarana, Marco; Reijmers, Rogier ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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