Early transcriptional changes after UVB treatment in atopic dermatitis include inverse regulation of IL-36γ and IL-37.
UVB
atopic dermatitis
inflammation
keratinocytes
microarray
Journal
Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
11
07
2020
revised:
26
09
2020
accepted:
12
10
2020
pubmed:
18
10
2020
medline:
23
2
2022
entrez:
17
10
2020
Statut:
ppublish
Résumé
Phototherapy with narrow-band Ultraviolet B (nb-UVB) is a major therapeutic option in atopic dermatitis (AD), yet knowledge of the early molecular responses to this treatment is lacking. The objective of this study was to map the early transcriptional changes in AD skin in response to nb-UVB treatment. Adult patients (n = 16) with AD were included in the study and scored with validated scoring tools. AD skin was irradiated with local nb-UVB on day 0, 2 and 4. Skin biopsies were taken before and after treatment (day 0 and 7) and analysed for genome-wide modulation of transcription. When examining the early response after three local UVB treatments, gene expression analysis revealed 77 significantly modulated transcripts (30 down- and 47 upregulated). Among them were transcripts related to the inflammatory response, melanin synthesis, keratinization and epidermal structure. Interestingly, the pro-inflammatory cytokine IL-36γ was reduced after treatment, while the anti-inflammatory cytokine IL-37 increased after treatment with nb-UVB. There was also a modulation of several other mediators involved in inflammation, among them defensins and S100 proteins. This is the first study of early transcriptomic changes in AD skin in response to nb-UVB. We reveal robust modulation of a small group of inflammatory and anti-inflammatory targets, including the IL-1 family members IL36γ and IL-37, which is evident before any detectable changes in skin morphology or immune cell infiltrates. These findings provide important clues to the molecular mechanisms behind the treatment response and shed light on new potential treatment targets.
Substances chimiques
Defensins
0
IL36G protein, human
0
IL37 protein, human
0
Interleukin-1
0
S100 Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
249-261Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Wollenberg A, Barbarot S, Bieber T, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.. J Eur Acad Dermatol Venereol. 2018;32:850-878.
Bieber T, Atopic dermatitis.. Ann Dermatol. 2010;22:125-137.
Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD, Atopic dermatitis.. Nat Rev Dis Primers. 2018;4:1.
Deckers IA, McLean S, Linssen S, Mommers M, van Schayck CP, Sheikh A, Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review of epidemiological studies.. PLoS One. 2012;7:e39803.
Gambichler T, Management of atopic dermatitis using photo(chemo)therapy. Arch Dermatol Res. 2009;301:197-203.
Garritsen FM, Brouwer MW, Limpens J, Spuls PI, Photo(chemo)therapy in the management of atopic dermatitis: an updated systematic review with implications for practice and research. Br J Dermatol. 2014;170:501-513.
Vakeva L, Niemela S, Lauha M, et al. Narrowband ultraviolet B phototherapy improves quality of life of psoriasis and atopic dermatitis patients up to 3 months: Results from an observational multicenter study. Photodermatol Photoimmunol Photomed. 2019;35:332-338.
Breuckmann F, von Kobyletzki G, Avermaete A, et al. Mechanisms of apoptosis: UVA1-induced immediate and UVB-induced delayed apoptosis in human T cells in vitro. J Eur Acad Dermatol Venereol. 2003;17:418-429.
Krutmann J, Morita A, Mechanisms of ultraviolet (UV) B and UVA phototherapy. J Investig Dermatol Symp Proc. 1999;4:70-72.
D'Orazio J, Jarrett S, Amaro-Ortiz A, Scott T, UV radiation and the skin. Int J Mol Sci. 2013;14:12222-12248.
Jekler J, Larko O, Combined UVA-UVB versus UVB phototherapy for atopic dermatitis: a paired-comparison study. J Am Acad Dermatol. 1990;22:49-53.
Patrizi A, Raone B, Ravaioli GM, Safety and Efficacy of Phototherapy in the Management of Eczema. Adv Exp Med Biol. 2017;996:319-331.
Gambichler T, Skrygan M, Tomi NS, Altmeyer P, Kreuter A, Changes of antimicrobial peptide mRNA expression in atopic eczema following phototherapy. Br J Dermatol. 2006;155:1275-1278.
Hong SP, Kim MJ, Jung MY, et al. Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement. J Invest Dermatol. 2008;128:2880-2887.
Suarez-Farinas M, Tintle SJ, Shemer A, et al. Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities. J Allergy Clin Immunol. 2011;127:954-964.
Tintle S, Shemer A, Suarez-Farinas M, et al. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response. J Allergy Clin Immunol. 2011;128:583-593.
Hanifin JM, Diagnostic features of atopic dermatitis. Acta Derm Venereol (Suppl). 1980;92:44-47.
Kunz B, Oranje AP, Labreze L, Stalder JF, Ring J, Taieb A, Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1997;195:10-19.
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M, The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001;10:11-18.
Charman CR, Venn AJ, Williams HC, The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients' perspectiv. Arch Dermatol. 2004;140:1513-1519.
Finlay AY, Khan GK, Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19:210-216.
Gordon PM, Saunders PJ, Diffey BL, Farr PM, Phototesting prior to narrowband (TL-01) ultraviolet B phototherapy. Br J Dermatol. 1998;139:811-814.
Schmittgen TD, Livak KJ, Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101-1108.
Bankhead P, Loughrey MB, Fernández JA, et al. QuPath: Open source software for digital pathology image analysis. Sci Rep. 2017;7:16878.
Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676-682.
Carpenter AE, Jones TR, Lamprecht MR, et al. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol. 2006;7:R100.
Ashburner M, Ball CA, Blake JA, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25:25-29.
Mi H, Muruganujan A, Huang X, et al. Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0). Nat. Protoc.. 2019;14:703-721.
Ghosh D, Ding L, Sivaprasad U, et al. Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways. PLoS One. 2015;10:e0144316.
Ewald DA, Malajian D, Krueger JG, et al. Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature ing the involvement of atherosclerosis and lipid metabolism pathways. BMC Med Genomics. 2015;8:60.
Tsoi LC, Rodriguez E, Stolzl D, et al. Progression of acute-to-chronic atopic dermatitis is associated with quantitative rather than qualitative changes in cytokine responses. J Allergy Clin Immunol. 2019;145:1406-1415.
Guttman-Yassky E, Ungar B, Malik K, et al. Molecular signatures order the potency of topically applied anti-inflammatory drugs in patients with atopic dermatitis. J Allergy Clin Immunol. 2017;140:1032-1042.
Bissonnette R, Pavel AB, Diaz A, et al. Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial. J Allergy Clin Immunol. 2019;144:1274-1289.
Foster AM, Baliwag J, Chen CS, et al. IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin.. J Immunol. 2014;192:6053-6061.
Bassoy EY, Towne JE, Gabay C, Regulation and function of interleukin-36 cytokines. Immunol Rev. 2018;281:169-178.
Ding L, Wang X, Hong X, Lu L, Liu D, IL-36 cytokines in autoimmunity and inflammatory disease. Oncotarget. 2018;9:2895-2901.
Bridgewood C, Fearnley GW, Berekmeri A, et al. IL-36gamma Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis. Front Immunol. 2018;9:200.
Braegelmann J, D'Erme AM, Akmal S, Maier J, Braegelmann C, Wenzel J, Interleukin-36gamma (IL-1F9) Identifies Psoriasis Among Patients With Erythroderma. Acta Derm Venereol. 2016;96:386-387.
D'Erme AM, Wilsmann-Theis D, Wagenpfeil J, et al. IL-36gamma (IL-1F9) is a biomarker for psoriasis skin lesions. J Invest Dermatol. 2015;135:1025-1032.
Johnston A, Xing X, Guzman AM, et al. IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression. J Immunol. 2011;186:2613-2622.
Keermann M, Koks S, Reimann E, Prans E, Abram K, Kingo K, Transcriptional landscape of psoriasis identifies the involvement of IL36 and IL36RN. BMC Genom.. 2015;16:322.
Hessam S, Sand M, Gambichler T, Skrygan M, Ruddel I, Bechara FG, Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop. Br J Dermatol. 2018;178:761-767.
Furue K, Ito T, Tanaka Y, et al. Cyto/chemokine profile of in vitro scratched keratinocyte model: Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon. J Dermatol Sci. 2019;94:244-251.
Otobe S, Sugaya M, Nakajima R, et al. Increased interleukin-36gamma expression in skin and sera of patients with atopic dermatitis and mycosis fungoides/Sezary syndrome. J Dermatol. 2018;45:468-471.
Bachelez H, Choon SE, Marrakchi S, et al. Inhibition of the Interleukin-36 Pathway for the Treatment of Generalized Pustular Psoriasis. N Engl J Med. 2019;380:981-983.
Wang L, Quan Y, Yue Y, Heng X, Che F, Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy. Oncol Lett. 2018;15:4711-4719.
Lachner J, Mlitz V, Tschachler E, Eckhart L, Epidermal cornification is preceded by the expression of a keratinocyte-specific set of pyroptosis-related genes. Sci Rep. 2017;7:17446.
Li S, Amo-Aparicio J, Neff CP, et al. Role for nuclear interleukin-37 in the suppression of innate immunity.. Proc Natl Acad Sci USA. 2019;116, 4456-4461.
Dinarello CA, Nold-Petry C, Nold M, et al. Suppression of innate inflammation and immunity by interleukin-37.. Eur J Immunol. 2016;46:1067--1081.
Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA, IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010;11:1014-1022.
Glaser R, Navid F, Schuller W, et al. UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo. J Allergy Clin Immunol. 2009;123:1117-1123.
Kennedy Crispin M, Fuentes-Duculan J, Gulati N, et al. Gene Profiling of Narrowband UVB-Induced Skin Injury Defines Cellular and Molecular Innate Immune Responses. J Invest Dermatol. 2013;133:692-701.
Nousbeck J, Ishida-Yamamoto A, Bidder M, et al. IGFBP7 as a potential therapeutic target in Psoriasis.. J Invest Dermatol. 2011;131:1767-1770.
Konig K, Marth L, Roissant J, et al. The plexin C1 receptor promotes acute inflammation. Eur J Immunol. 2014;44:2648-2658.
Ertugrul G, Keles D, Oktay G, Aktan S, Matrix metalloproteinase-2 and -9 activity levels increase in cutaneous lupus erythematosus lesions and correlate with disease severity. Arch Dermatolog Res. 2018;310:173-179.
Hao L, Zhu G, Lu Y, et al. Deficiency of cathepsin K prevents inflammation and bone erosion in rheumatoid arthritis and periodontitis and reveals its shared osteoimmune role. FEBS Lett. 2015;589:1331-1339.
Jiang F, Gao Y, Dong C, Xiong S, ODC1 inhibits the inflammatory response and ROS-induced apoptosis in macrophages. Biochem Biophys Res Commun. 2018;504:734-741.