Abstract
Skin is protected by a tough but flexible multilayered barrier and is a front line for immune responses against invading particles. For many years now, skin has been a tissue where certain vaccines are injected for the prevention of infectious disease, however, the detailed mechanisms of the skin immune response are not yet well understood. Using thin and small injection needles, we carefully injected OVA into a restricted region of mouse skin, i.e., intradermal (ID), and examined the antibody response in comparison with subcutaneous (SC) injection or epicutaneous patch administration of OVA. Epicutaneous patches induced a high IgE response against OVA, but IgG production was low. High IgG production was induced by both ID and SC injection, moreover, ID injection induced higher IgG production without any adjutants. Furthermore, OVA-specific IgE production was diminished by ID injection. We found that ID injection could efficiently stimulate skin resident DCs, drive Th1-biased conditions and diminish IgE production. The ID injection response was regulated by Langerin+ dermal DCs, because OVA was taken up mainly by these cells and, after transiently deleting them, the IgE response was no longer diminished and IgG1 production was enhanced. We also tested whether ID injection might be an effective allergy treatment by attempting to inhibit ongoing IgE production in mice with experimentally induced high serum IgE levels. Multiple ID injections of OVA were shown to prevent elevation of serum OVA-specific IgE after repeated allergen challenge. In contrast, SC OVA injection could only transiently inhibit the OVA-specific IgE production. These findings indicated that ID injection results in higher induction of antigen-specific IgG, and thus may be useful for vaccine delivery with little or no adjuvant components. Moreover, the observed diminishment of IgE and induction of Th1-biased immune responses suggest that ID may be a useful injection route for allergy immunotherapy.
Highlights
Skin is an enormous organ that separates the outside world from our bodies
We found that antigen delivery by ID injection can induce better antigen-specific IgG production than SC injection, and that antigen-specific IgE production is diminished by ID injection
We found that Langerin+ dendritic cells (DC) were more plentiful in ID antigen-injected mice than in SC injected mice
Summary
Skin is an enormous organ that separates the outside world from our bodies It is flexible, and has a distinct barrier function to block penetration of external foreign particles and prevents excessive water loss [1, 2]. Has a distinct barrier function to block penetration of external foreign particles and prevents excessive water loss [1, 2] To perform these functions, our skin is composed of multiple layers, hair, stratum corneum, stratified epidermal cell layer, dermal connective tissue layer, sub-dermal, looser connective tissue layer, fat layer, and skin muscle. Parasites can penetrate deeply into the skin as a result of bites by their vectors, such as mosquitoes or ticks, and induce distinct immune responses [7]. These various invaders that break through our skin barrier system are recognized and rejected by physical or immunological reactions in a manner appropriate for each of them
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