Ultraviolet radiation-induced upregulation of antimicrobial proteins in health and disease

Felton, Sarah; Navid, Fatemeh; Schwarz, Agatha; Schwarz, Thomas; Gläser, Regine; Rhodes, Lesley E.

doi:10.1039/c2pp25158b

Cited by 35 publications

(43 citation statements)

References 51 publications

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“…Although photosensitive areas are generally affected by SCLE, photoprotected areas can also be involved, suggesting that commensal colonization patterns could play a role in the absence of UV exposure. UV light is known to not only trigger keratinocyte apoptosis and exposure of endogenous Ro60 on the cell surface in apoptotic blebs (52) but also induce antimicrobial peptides (53). These peptides are well known to cause dysbiosis via alterations of the community structure of microbiota (54).…”

Section: Discussionmentioning

confidence: 99%

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

et al. 2018

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The earliest autoantibodies in lupus are directed against the RNA binding autoantigen Ro60, but the triggers against this evolutionarily conserved antigen remain elusive. We identified Ro60 orthologs in a subset of human skin, oral, and gut commensal bacterial species and confirmed the presence of these orthologs in patients with lupus and healthy controls. Thus, we hypothesized that commensal Ro60 orthologs may trigger autoimmunity via cross- reactivity in genetically susceptible individuals. Sera from human anti-Ro60–positive lupus patients immunoprecipi-tated commensal Ro60 ribonucleoproteins. Human Ro60 autoantigen–specific CD4 memory T cell clones from lupus patients were activated by skin and mucosal Ro60-containing bacteria, supporting T cell cross-reactivity in humans. Further, germ-free mice spontaneously initiated anti-human Ro60 T and B cell responses and developed glomerular immune complex deposits after monocolonization with a Ro60 ortholog–containing gut commensal, linking anti- Ro60 commensal responses in vivo with the production of human Ro60 autoantibodies and signs of autoimmunity. Together, these data support that colonization with autoantigen ortholog-producing commensal species may initiate and sustain chronic autoimmunity in genetically predisposed individuals. The concept of commensal ortholog cross-reactivity may apply more broadly to autoimmune diseases and lead to novel treatment approaches aimed at defined commensal species.

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Section: Discussionmentioning

confidence: 99%

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

et al. 2018

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“…Antimicrobial peptides seem to have a role in the pathogenesis of skin inflammation in psoriasis (21,30).…”

Section: Narrow-band Uvb (Nb-uvb) Doses Serum 25-hydroxyvitamin D (2mentioning

confidence: 99%

Narrow-band Ultraviolet B Treatment Boosts Serum 25-hydroxyvitamin D in Patients with Psoriasis on Oral Vitamin D Supplementation

Ala‐Houhala

Karppinen²,

Vähävihu³

et al. 2014

Acta Derm Venerol

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A course of treatment with narrow-band ultraviolet B (NB-UVB) improves psoriasis and increases serum 25-hydroxyvitamin D (25(OH)D). In this study 12 patients with psoriasis who were supplemented with oral cholecalciferol, 20 µg daily, were given a course of NB-UVB and their response measured. At baseline, serum 25(OH)D was 74.14 ± 22.9 nmol/l. At the 9th exposure to NB-UVB 25(OH)D had increased by 13.2 nmol/l (95% confidence interval (95% CI) 7.2-18.4) and at the 18th exposure by 49.4 nmol/l (95% CI 35.9-64.6) above baseline. Psoriasis Area Severity Index score improved from 8.7 ± 3.5 to 4.5 ± 2.0 (p < 0.001). At baseline, psoriasis lesions showed low vitamin D metabolizing enzyme (CYP27A1, CYP27B1) and high human β-defensin-2 mRNA expression levels compared with those of the healthy subjects. In conclusion, NB-UVB treatment significantly increases serum 25(OH)D in patients with psoriasis who are taking oral vitamin D supplementation, and the concentrations remain far from the toxicity level. Healing psoriasis lesions show similar mRNA expression of vitamin D metabolizing enzymes, but higher antimicrobial peptide levels than NB-UVB-treated skin in healthy subjects.

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“…We propose that in patients with CIS, exposure to narrow band UVB will similarly alter the immunogenic properties of circulating DCs and their precursor cells toward a regulatory profile. As UVB exposure can simulate innate immunity (61), we do not anticipate detrimental effects of the narrowband UVB phototherapy on host responses to infection.…”

Section: Proposed Mechanism Of Prevention Of Ms Development By Uvb Phmentioning

confidence: 99%

Narrowband UVB Phototherapy for Clinically Isolated Syndrome: A Trial to Deliver the Benefits of Vitamin D and Other UVB-Induced Molecules

et al. 2017

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Low vitamin D and insufficient sun exposure are additive independent risk factors for the development of multiple sclerosis (MS). The usual measure of vitamin D status, serum 25-hydroxy vitamin D [25(OH)D], is also a marker of recent exposure to the UVB rays of sunshine. The main evidence for a protective effect for MS development of higher 25(OH)D comes from observational studies, but this study design cannot separate out whether 25(OH)D is acting as a marker of vitamin D status, sun exposure, or both. In light of a lack of definitive outcomes in MS patients after trials of vitamin D supplementation and the ability of narrowband UVB to induce vitamin D, as well as other immune-regulatory molecules in skin, the Phototherapy for Clinically Isolated Syndrome (PhoCIS) trial was established to investigate the benefits of narrowband UVB, in addition to supplemented vitamin D, on MS development in individuals with Clinically Isolated Syndrome. We propose that the PhoCIS trial provides a fresh approach to re-defining the reported associations of 25(OH)D levels with MS development and progression.

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Ultraviolet radiation-induced upregulation of antimicrobial proteins in health and disease

Cited by 35 publications

References 51 publications

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

Narrow-band Ultraviolet B Treatment Boosts Serum 25-hydroxyvitamin D in Patients with Psoriasis on Oral Vitamin D Supplementation

Narrowband UVB Phototherapy for Clinically Isolated Syndrome: A Trial to Deliver the Benefits of Vitamin D and Other UVB-Induced Molecules

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