Blunted epidermal L‐tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 2: epidermal H₂O₂/ONOO^–‐mediated stress in vitiligo hampers indoleamine 2,3‐dioxygenase and aryl hydrocarbon receptor‐mediated immune response signaling

Abstract

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The Aryl Hydrocarbon Receptor in Barrier Organ Physiology, Immunology, and Toxicology

“…UV light generates the high-affinity ligand FICZ from tryptophan. In addition, hydrogen peroxide in skin of vitiligo patients can lead to formation of FICZ (Schallreuter et al, 2012). Common skin-resident yeasts, Malassezia spp., produce the AhR ligands FICZ, ICZ, pityriacitrin, and malassezin (Wille et al, 2001;Gaitanis et al, 2008;Magiatis et al, 2013).…”

“…UV light induces CYP1A1 in human skin (Katiyar et al, 2000) and cultured human keratinocytes (Wei et al, 1999;Fritsche et al, 2007). Furthermore, the proposed endogenous AhR ligand FICZ has been detected in UVB-irradiated immortal human keratinocytes , in skin samples from vitiligo patients (Schallreuter et al, 2012), and in skin from patients with seborrheic dermatitis carrying commensal yeasts belonging to the genus Malassezia, which converts tryptophan to several AhR-activating compounds (Magiatis et al, 2013).…”

“…In fact, the catalytic efficiency of CYP1A1 for FICZ is close to the limit of diffusion (Wincent et al, 2009). FICZ has been identified in human skin (Wincent et al, 2009;Schallreuter et al, 2012;Magiatis et al, 2013), and FICZ-derived sulfate conjugates have been detected in human urine (Wincent et al, 2009). The current data suggest that FICZ can be formed via different pathways that lead to formation of indole-3-acetaldehyde, the precursor of FICZ, such as enzymatic deamination of tryptamine and oxidation of tryptophan by intracellular oxidants (Rannug et al, unpublished data).…”

Oxidized tyrosinase: A possible antigenic stimulus for non-segmental vitiligo autoantibodies

“…Over the years, multiple aspects of biochemical, immunological and other biological aspects that play a role in the pathogenesis of vitiligo have been studied [1][2][3][4][5][6][7]. For the last decade or so, the potential role of ROS in vitiligo patients was extensively studied by Schallreuter and colleagues [13][14][15][16][29][30][31][32][33]. Now it has well been recognized as a model disease for H 2 O 2 and/or peroxynitrite (ONOO À )-mediated oxidative stress [13][14][15][16][29][30][31][32][33].…”

“…Now it is well known that due to oxidative stress, numerous proteins in addition to tyrosinase are affected in vitiligo [12]. Excess generation of hydrogen peroxide (H 2 O 2 ) and its associated uncontrollable oxidative stress have also been well documented in vitiligo [13][14][15][16]. It is also known that generation of H 2 O 2 has been attributed to its intrinsic release from the melanogenesis pathway, ultimately yielding apoptosis of melanocytes [13,17].…”