A deep dive into UV-based phototherapy: Mechanisms of action and emerging molecular targets in inflammation and cancer

摘要

UV-based phototherapy (including psoralen plus UVA (PUVA), UVB and UVA1) has a long, successful history in the management of numerous cutaneous disorders. Photoresponsive diseases are etiologically diverse, but most involve disturbances in local (and occasionally systemic) inflammatory cells and/or abnormalities in keratinocytes that trigger inflammation. UV-based phototherapy works by regulating the inflammatory compo-nent and inducing apoptosis of pathogenic cells. This results in a fascinating and complex network of simulta-neous events-immediate transcriptional changes in keratinocytes, immune cells, and pigment cells; the emergence of apoptotic bodies; and the trafficking of antigen-presenting cells in skin-that quickly transform the microenvironment of UV-exposed skin. Molecular elements in this system of UV recognition and response include chromophores, metabolic byproducts, innate immune receptors, neurotransmitters and mediators such as chemokines and cytokines, antimicrobial peptides, and platelet activating factor (PAF) and PAF-like mol-ecules that simultaneously shape the immunomodulatory effects of UV and their interplay with the microbiota of the skin and beyond. Phototherapy's key effects-proapoptotic, immunomodulatory, antipruritic, antifibrotic, propigmentary, and pro-prebiotic-promote clinical improvement in various skin diseases such as psoriasis, atopic dermatitis (AD), graft-versus-host disease (GvHD), vitiligo, scleroderma, and cutaneous T-cell lymphoma (CTCL) as well as prevention of polymorphic light eruption (PLE). As understanding of phototherapy improves, new therapies (UV-and non-UV-based) are being developed that will modify regulatory T-cells (Treg), interact with (resident) memory T-cells and /or utilize agonists and antagonists as well as antibodies targeting soluble molecules such as cytokines and chemokines, transcription factors, and a variety of membrane-associated receptors. (C) 2020 Elsevier Inc. All rights reserved.