Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa

被引：83

作者：

Zouboulis, C. C. ^{[1
,2
,3
,4
,5
]}

da Costa, A. Nogueira ^{[6
,11
]}

Makrantonaki, E. ^{[1
,2
,3
,4
,12
]}

Hou, X. X. ^{[1
,2
,3
,4
]}

Almansouri, D. ^{[1
,2
,3
,4
]}

Dudley, J. T. ^{[7
]}

Edwards, H. ^{[6
]}

Readhead, B. ^{[7
,13
]}

Balthasar, O. ^{[8
]}

Jemec, G. B. E. ^{[5
,9
]}

Bonitsis, N. G. ^{[1
,2
,3
,4
]}

Nikolakis, G. ^{[1
,2
,3
,4
,5
]}

Trebing, D. ^{[1
,2
,3
,4
]}

Zouboulis, K. C. ^{[10
]}

Hossini, A. M. ^{[1
,2
,3
,4
]}

机构：

[1] Dessau Med Ctr, Brandenburg Med Sch Theodor Fontane, Dept Dermatol, Dessau, Germany

[2] Dessau Med Ctr, Brandenburg Med Sch Theodor Fontane, Dept Venereol, Dessau, Germany

[3] Dessau Med Ctr, Brandenburg Med Sch Theodor Fontane, Dept Allergol, Dessau, Germany

[4] Dessau Med Ctr, Brandenburg Med Sch Theodor Fontane, Dept Immunol, Dessau, Germany

[5] European Hidradenitis Suppurat Fdn eV, Dessau, Germany

[6] UCB Bioprod SA, Translat Med, Slough, Berks, England

[7] Icahn Sch Med Mt Sinai, Inst Next Generat Healthcare, Dept Genet & Genom Sci, New York, NY 10029 USA

[8] Dessau Med Ctr, Inst Pathol, Dessau, Germany

[9] Univ Copenhagen, Zealand Univ Hosp, Dept Dermatol, Roskilde, Denmark

[10] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, ETH Zurich, Zurich, Switzerland

[11] AstraZeneca, Oncol R&D Org, Precis Med, Molndal, Sweden

[12] Ulm Univ, Dept Dermatol & Allergol, Ulm, Germany

[13] Arizona State Univ, Banner Neurodegenerat Dis Res Ctr, Tempe, AZ USA

来源：

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY | 2020年 / 34卷 / 04期

关键词：

PROLINE-RICH PROTEINS; EXPRESSION; SKIN; INVERSA; DISEASE; INFLAMMATION; CARCINOMA; BARRIER; HEALTH; MIGRATION;

D O I：

10.1111/jdv.16147

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Background The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting. Objective Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. Methods Hidradenitis suppurativa/acne inversa molecular taxonomy and key signalling pathways were studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non-lesional skin obtained from female HS patients and matched healthy controls using the Agilent array platform. The differential gene expression was confirmed by quantitative real-time PCR and targeted protein characterization via immunohistochemistry in another set of female patients. HS-involved skin compartments were also recognized by immunohistochemistry. Results Alterations to key regulatory pathways involving glucocorticoid receptor, atherosclerosis, HIF1 alpha and IL17A signalling as well as inhibition of matrix metalloproteases were detected. From a functional standpoint, cellular assembly, maintenance and movement, haematological system development and function, immune cell trafficking and antimicrobial response were key processes probably being affected in HS. Sixteen genes were found to characterize HS from a molecular standpoint (DEFB4, MMP1, GJB2, PI3, KRT16, MMP9, SERPINB4, SERPINB3, SPRR3, S100A8, S100A9, S100A12, S100A7A (15), KRT6A, TCN1, TMPRSS11D). Among the proteins strongly expressed in HS, calgranulin-A, calgranulin-B and serpin-B4 were detected in the hair root sheath, koebnerisin and connexin-32 in stratum granulosum, transcobalamin-1 in stratum spinosum/hair root sheath, small prolin-rich protein-3 in apocrine sweat gland ducts/sebaceous glands-ducts and matrix metallopeptidase-9 in resident monocytes. Conclusion Our findings highlight a panel of immune-related drivers in HS, which influence innate immunity and cell differentiation in follicular and epidermal keratinocytes as well as skin glands.

引用

页码：846 / 861

页数：16

共 73 条

[1] Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa [J].