<p class="first" id="d4692520e67">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 component and inducing
apoptosis of pathogenic cells. This results in a fascinating and complex network of
simultaneous 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
molecules 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.
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