A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin

Skin codelivery of contact sensitizers and neurokinin-1 receptor antagonists integrated in microneedle arrays suppresses allergic contact dermatitis

“…These data indicate that the immunosuppressive effects of NK1R antagonists in CHS depend at least in part on an imbalance between stimulatory and suppressive skin DC homed in skin-dLN. 20,48 In addition, our results from in vivo experiments in which LC were depleted confirmed that LC are necessary for the effect of the NK1R antagonist-based MNA immunosuppressive approach. Experiments beyond the scope of this study will determine the individual roles of specific NK1R signaling in different subsets of skin DC.…”

“…To track the Ag applied to the skin, we used MNA loaded with OVA conjugated to the fluorochrome Texas Red (OVATR-MNA) alone or with RP67580 (OVATR-RP67580-MNA). Because IL-10 has been associated with the immunosuppressive capacity of DC, 20,47,48 these experiments were done in IL-10-enhanced green fluorescent protein (EGFP) reporter B6 mice in which EGFP expression is driven by the endogenous IL-10 promoter. OVATR-MNA, OVATR-RP67580-MNA, or empty-MNA were applied to the ears of IL-10-EGFP mice, and cell suspensions of skin-dLN were analyzed by flow cytometry 2 days later.…”

“…Our findings indicate that delivery of Ag and NK1R antagonist to the skin via MNA reduces the number of dermal DC transporting Ag to skin-dLN without affecting the quantity of LC bearing allergen and IL-10. 20,48 Thus, we tested if LC have a role in the inhibitory effect of the NK1R antagonists in hu-Lang-DTR mice, a model that allows selective depletion of epidermal LC by administration of DT. 20 Three days after DT injection, when epidermal LC were depleted (Fig E6 , D), hu-Lang-DTR mice were sensitized with OVA-MNA, OVA-RP67580-MNA, or empty-MNA on the ear skin and elicited with OVA injected i.d.…”

Current Progress in Particle-Based Systems for Transdermal Vaccine Delivery

“…Langerhans cells are uniquely located in the epidermal layer and build up the first line of APCs that encounter skin-invading antigens. A multitude of scientific reports indicate a crucial role for LCs in the induction of CD8 + T-cell responses, likely due to their ability to cross-present antigens to naïve or memory CD8 + T cells (3). The development and employment of inducible transgenic rodent models (e.g., the Langerin-DTR mouse model) recently challenged the essential need for LCs as antigen-presenting cells in the skin and emphasized the importance of dermal dendritic cells (dDCs) (4,5).…”

Microneedles for painless transdermal immunotherapeutic applications

“…This opens up a new avenue for immunotherapy of diseases without causing noticeable adverse effects [180]. For example, Burg et al designed microprojection arrays (MPA) in polycarbonate material through a hot embossing procedure and coated OVA onto the surface of the MPAs [181]. In this study, they found that slit-MPAs (110 μm ± 3 μm tall projections at 7k p/cm 2 ) with higher tip surface areas than conical-MPAs (207 μm ± 5 μm tall projections at 10,000 (10k) projections/cm 2 (p/cm 2 )) were more suitable for only epidermal delivery using low application energies.…”