Bedoui S, Whitney PG, Waithman J et al.Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat Immunol 10:488-495

The Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
Nature Immunology (Impact Factor: 20). 05/2009; 10(5):488-95. DOI: 10.1038/ni.1724
Source: PubMed


Skin-derived dendritic cells (DCs) include Langerhans cells, classical dermal DCs and a langerin-positive CD103(+) dermal subset. We examined their involvement in the presentation of skin-associated viral and self antigens. Only the CD103(+) subset efficiently presented antigens of herpes simplex virus type 1 to naive CD8(+) T cells, although all subsets presented these antigens to CD4(+) T cells. This showed that CD103(+) DCs were the migratory subset most efficient at processing viral antigens into the major histocompatibility complex class I pathway, potentially through cross-presentation. This was supported by data showing only CD103(+) DCs efficiently cross-presented skin-derived self antigens. This indicates CD103(+) DCs are the main migratory subtype able to cross-present viral and self antigens, which identifies another level of specialization for skin DCs.

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    • "In the mouse, a consistent body of evidence indicates a dominating contribution of lymph-noderesident CD8 + DCs in cross-presentation (Pooley et al, 2001; Joffre et al, 2012). However, skin DCs such as epidermal Langerhans cells (LCs) (Stoitzner et al, 2006; Flacher et al, 2010) and Langerin + dermal DCs (dDCs) (Bedoui et al, 2009; Henri et al, 2010) can also cross-present. In vivo, the relative involvement of skin DCs versus CD8 + DCs in priming efficient immune responses does not depend only on the targeted subset, but also on other factors, including the type, amount and formulation of antigen, the site of immunization, the endocytic route and intracellular degradation pathways, and the maturation signals received by DCs (Delamarre et al, 2003; Spörri & Reis e Sousa, 2005; Blander & Medzhitov, 2006; Tacken et al, 2007; Idoyaga et al, 2011; Chatterjee et al, 2012). "

    EMBO Molecular Medicine 12/2014; 6(12):1638-1638. · 8.67 Impact Factor
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    • "The death of antigen-carrying skin-derived DCs would also be expected to accelerate antigen transfer to LN-resident DCs. The priming capability of CD103−DDCs in relation to CD4+ T cells is higher than for CD8+ T cells44, while CD8α+ LN-resident DCs are known to be effective antigen-presenting cells for CD8+ T cells34445, with high phagocytic activity46. Thus, it is possible that the influx of a large number of apoptotic antigen-carrying CD103−DDCs triggers accelerated phagocytosis and cross priming by CD8α+ LN-resident DCs. "
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    ABSTRACT: Skin-derived dendritic cells (DCs) play a crucial role in the maintenance of immune homeostasis due to their role in antigen trafficking from the skin to the draining lymph nodes (dLNs). To quantify the spatiotemporal regulation of skin-derived DCs in vivo, we generated knock-in mice expressing the photoconvertible fluorescent protein KikGR. By exposing the skin or dLN of these mice to violet light, we were able to label and track the migration and turnover of endogenous skin-derived DCs. Langerhans cells and CD103(+)DCs, including Langerin(+)CD103(+)dermal DCs (DDCs), remained in the dLN for 4-4.5 days after migration from the skin, while CD103(-)DDCs persisted for only two days. Application of a skin irritant (chemical stress) induced a transient >10-fold increase in CD103(-)DDC migration from the skin to the dLN. Tape stripping (mechanical injury) induced a long-lasting four-fold increase in CD103(-)DDC migration to the dLN and accelerated the trafficking of exogenous protein antigens by these cells. Both stresses increased the turnover of CD103(-)DDCs within the dLN, causing these cells to die within one day of arrival. Therefore, CD103(-)DDCs act as sentinels against skin invasion that respond with increased cellular migration and antigen trafficking from the skin to the dLNs.
    Scientific Reports 08/2014; 4:6030. DOI:10.1038/srep06030 · 5.58 Impact Factor
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    • "In the epidermis, Langerhans cells (LC) form a dense network of DC capable of capturing antigen and migrating to the LN after traversing the basement membrane into the dermis. In mice, LC appear to be particularly efficient at tolerance induction and the formation of regulatory T cells (Tregs) (6, 7), whereas they are dispensable for induction of CD8 T cell responses to infections (8–10). Skin macrophages also populate the dermis and include perivascular macrophages that are distributed along post-capillary venules and can assist with the recruitment of neutrophils from the blood (11). "
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    ABSTRACT: The skin is a large and complex organ that acts as a critical barrier protecting the body from pathogens in the environment. Numerous heterogeneous populations of immune cells are found within skin, including some that remain resident and others that can enter and exit the skin as part of their migration program. Pathogen-specific CD8(+) T cells that persist in the epidermis following infection are a unique population of memory cells with important roles in immune surveillance and protective responses to reinfection. How these tissue-resident memory T cells form in the skin, the signals controlling their persistence and behavior, and the mechanisms by which they mediate local recall responses are just beginning to be elucidated. Here, we discuss recent progress in understanding the roles of these skin-resident T cells and also highlight some of the key unanswered questions that need addressing.
    Frontiers in Immunology 07/2014; 5:332. DOI:10.3389/fimmu.2014.00332
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