The skin as an immune organ: Tolerance versus effector responses and applications to food allergy and hypersensitivity reactions

Abstract

Skin is replete with immunocompetent cells that modulate signaling pathways to maintain a salubrious immunogenic/ tolerogenic balance. This fertile immune environment plays a significant role in the development of allergic responses and sensitivities, but the mechanisms underlying these pathways have been underappreciated and underused with respect to developing therapeutics. Among the complex repertoire of cells that promote tolerogenic pathways in the periphery, 2 key classes include dendritic cells and regulatory T (Treg) cells. Immature dendritic cells are the first line of defense, patrolling the periphery, sampling antigens, and secreting cytokines that suppress immune cells and promote the survival of Treg cells. Skin-homing Treg cells also play a critical role in mitigating the reactivity of immune cells, secreting high levels of cytokines that promote tolerance. Therapeutic approaches that capitalize on our knowledge of the rich cellular and molecular environment are emerging and show great promise. We will discuss the advantages and challenges of 5 such strategies and how these therapies might mitigate the atopic march by facilitating tolerance. We conclude that skin is a multifaceted structure that provides a fertile ground for therapeutic discovery. Accordingly, ongoing work in this domain will no doubt continue to deliver exciting progress for improved health outcomes. (J Allergy Clin Immunol 2019;144:362-74.)

Modulating Shrimp Tropomyosin-Mediated Allergy: Hypoallergen DNA Vaccines Induce Regulatory T Cells to Reduce Hypersensitivity in Mouse Model

“…Together with our adoptive transfer data, this revitalizes the capacity of pMED171 in inducing and maintaining tolerogenic immune responses, initially from peripheral locales then to the site of allergen exposure, that drive the overall protection against shrimp allergy. Our data also support intradermal delivery as a preferred route due to the high frequency of cutaneous DC and skin DC as the only cell populations with migratory behavior to drive tolerance at the site of allergen exposure [45,46]. It is noteworthy that naked pCI-Neo “treatment” neither promoted Treg cell responses, repressed IgE synthesis, nor inflammatory responses, but only increased nonspecific Th1 responses.…”

SingleCellSignalR: Inference of intercellular networks from single-cell transcriptomics

“…14). This striking observation strengthens the potential for an immune function of the epidermis (55,56) and may have essential implications in inflammatory skin diseases such as psoriasis or atopic dermatitis.…”

Research Progress in Atopic March

“…Mutations in the filaggrin gene ( FLG ) can impair the barrier function of the skin and induce an allergic response ( 42 , 43 ). Several studies have shown patients with impaired or reduced levels of filaggrin to be more susceptible to food sensitization ( 44 – 46 ). Moreover, FLG mutations increase the risk of early and severe AD and of AA in individuals who have had AD ( 47 – 49 ).…”