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Polymorphic light eruption (PLE) has been mechanistically linked to cytokine abnormalities. Emerging preclinical evidence posits the skin microbiome as a critical modulator of ultraviolet (UV)-induced cytokine expression, thereby influencing subsequent immune responses. This intricate relationship remains underexplored in the context of PLE. Hence, we investigated the differential responses between disinfected and non-disinfected skin following both single and repetitive exposures to solar-simulated UV radiation in patients with PLE. An experimental, half-body pilot study was conducted involving six PLE patients and 15 healthy controls. Participants' skin was exposed to single and multiple doses of solar-simulated UV radiation, both in disinfected and in non-disinfected skin areas. The co-primary outcomes were PLE score and cytokine expression in blister fluid analysed through OLINK proteomic profiling. Secondary outcomes were erythema, pigmentation, induction of apoptotic cells in vacuum-generated suction blisters, and density of infiltrate in skin biopsies of PLE patients. Among the 71 cytokines analysed, baseline expression levels of 20 specific cytokines-integral to processes such as apoptosis, inflammation, immune cell recruitment, cellular growth, and differentiation-were significantly impaired in PLE patients compared with healthy controls. Notably, skin disinfection reversed the observed cytokine imbalances following a single UV exposure at the minimal erythema dose (MED) level and exhibited even more pronounced effects after multiple UV exposures. However, no significant differences were evident in PLE score, erythema, pigmentation, or rates of apoptotic cell induction upon UV radiation. These findings provide evidence for UV-driven cytokine regulation by the skin microbiota and imply microbiome involvement in the PLE immune response., (© 2024 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Topical dithranol is effective in autoimmune conditions like alopecia areata, inducing hair regrowth in a high percentage of cases. Exact mechanisms of dithranol in alopecia areata, with seemingly healthy epidermis besides altered hair follicles, are not well understood. To better understand dithranol's mechanisms on healthy skin, we analysed its effect on normal murine as well as xenografted human skin. We found a strong increase in mRNA expression of anti-microbial peptides (AMPs) (eg Lcn2, Defb1, Defb3, S100a8, S100a9), keratinocyte differentiation markers (eg Serpinb3a, Flg, Krt16, Lce3e) and inflammatory cytokines (eg Il1b and Il17) in healthy murine skin. This effect was paralleled by inflammation and disturbed skin barrier, as well as an injury response resulting in epidermal hyperproliferation, as observed in murine and xenografted adult human skin. This contact response and disturbed barrier induced by dithranol might lead via a vicious loop between AMPs such as S100a8/a9 (that led to skin swelling itself after topical application) and cytokines such as IL-1β to an immune suppressive environment in the skin. A better understanding of the skin's physiologic response to dithranol may open up new avenues for the establishment of novel therapeutics (including AMP-related/interfering molecules) for certain skin conditions, such as alopecia areata., (© 2021 The Authors. Experimental Dermatology published by John Wiley & Sons.)

Psoriasis commonly responds beneficially to UV radiation from natural sunlight or artificial sources. Therapeutic mechanisms include the proapoptotic and immunomodulating effects of UV, affecting many cells and involving a variety of pro- and anti-inflammatory cytokines, downregulating the Th17/IL-23 response with simultaneous induction of regulatory immune cells. However, exposure to UV radiation in a subset of psoriasis patients leads to exacerbation of the disease. We herein shed light on the predisposing factors of photosensitive psoriasis, including genetics (such as HLA-Cw*0602 or CARD14), gender and coexisting photodermatoses such as polymorphic light eruption (PLE) in the context of potential molecular mechanisms behind therapeutic photoresponsiveness or photoaggravation. UV-induced damage/pathogen-associated molecular patterns, damage to self-coding RNA (signalling through Toll-like receptors), certain antimicrobial peptides and/or inflammasome activation may induce innate immunity, leading to psoriasis at the site of UV exposure when there is concomitant, predisposing resistance against UV-induced suppression of the adaptive immune response (like in PLE) that otherwise would act to reduce psoriasis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)