Skin as an immune organ and clinical applications of skin-based immunotherapy

Abstract

BackgroundThe prevalence of food allergy is increasing, and allergen avoidance continues to be the main standard of care. There is a critical need for safe and effective forms of immunotherapy for patients with food allergy as well as other allergic diseases.FindingsThe skin is a multifunctional organ with unique immunologic properties, making it a favorable administration route for allergen-specific immunotherapy. Epicutaneous immunotherapy (EPIT) takes advantage of the skin’s immune properties to modulate allergic responses and is thus one of the allergen-specific immunotherapy approaches currently being investigated for food allergy. Advances made in the understanding of how epicutaneously applied proteins interact with the immune system and in the technology for facilitating such interactions offer many opportunities for clinical application. Research has shown that allergen delivered to intact skin via EPIT is taken up in the superficial layers of the skin by Langerhans cells, avoiding passive movement of allergen through the dermis and limiting systemic circulation. EPIT brings about allergen desensitization by activating a population of regulatory T cells (Tregs) with unique properties and the potential for inducing a sustained effect as well as the possibility (seen in animal models) for protection against further sensitizations. Several clinical trials investigating the therapeutic efficacy of EPIT for treatment of peanut allergy have been completed, as well as a Phase 2 trial for treatment of milk allergy.ConclusionsTaken together, the reviewed literature supports the concept that EPIT activates the natural desensitization pathway of the skin, offering a progressive, possibly sustained response. EPIT offers a potential alternative for allergen immunotherapy that is less invasive and carries a lower risk for systemic reactions than oral immunotherapy.

Diverse Mechanisms of Allergen Specific Immunotherapy

“…Hence it is one of the allergen-specific immunotherapy approaches currently being investigated for rhino-conjunctivitis and food allergies [23]. EPIT requires depositing the allergen onto a patch with a surrounding adhesive [24]. Two different epicutaneous delivery systems were developed for the purpose of improving allergen skin penetration [23,25].…”

“…Thus, the allergen can reach the deep epidermis stratum and it is carried by Langerhans cells to local regional lymph nodes [23,26]. When compared to SCIT or OIT, application of allergen to intact skin is less invasive, without the need for injection or swallowing of an allergen [24]. EPIT is well tolerated, except that only mild skin irritation may occur at the patch site.…”

“…These cells are the centre of the immune regulatory effect and they inhibit Th2 cells. EPIT-induced Tregs also express a large repertoire of homing receptors suggesting that Tregs are able to migrate to various sites of allergen exposure (i.e., skin, lung and gut), suppress local immune responses to allergen stimulation, and potentially induce tolerance [24].…”

Transcutaneous delivery of DNA/mRNA for cancer therapeutic vaccination

“…The skin consists of the outermost stratum corneum (SC), an outer epidermis and an inner dermis (Figure ) . The SC consists of corneocytes and lipids forming a so‐called “brick‐and‐mortar” structure, which is largely responsible for the barrier against the transcutaneous delivery of various drugs.…”

“…The skin consists of the outermost stratum corneum (SC), an outer epidermis and an inner dermis ( Figure 2). 11 The SC consists of corneocytes and lipids forming a so-called "brick-and-mortar" structure, which is largely responsible for the barrier against the transcutaneous delivery of various drugs. Restricted by the '500 Dalton rule", 12 it is hard for vaccines including peptides, antigens and nucleic acids to penetrate the intact SC and reach the active epidermis and dermis.…”