TY - JOUR
T1 - Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa
AU - Zouboulis, C. C.
AU - Nogueira da Costa, A.
AU - Makrantonaki, E.
AU - Hou, X. X.
AU - Almansouri, D.
AU - Dudley, J. T.
AU - Edwards, H.
AU - Readhead, B.
AU - Balthasar, O.
AU - Jemec, G. B.E.
AU - Bonitsis, N. G.
AU - Nikolakis, G.
AU - Trebing, D.
AU - Zouboulis, K. C.
AU - Hossini, A. M.
N1 - Funding Information:
Funding source This work was partially funded by a research grant to Christos C. Zouboulis from the German Federal Ministry of Education and Research (BMBF) [Project 0313660 ‘Investigation of gene expression in apocrine glands of patients with acne inversa (hidradenitis suppurativa)’] and Unilever R & D, Port Sunlight, Birmingham, UK. ATLAS Biolabs, Berlin, Germany is recognized for microarray labelling, hybridization and scanning; Dr. M. Brunner and N. Stolze, Depts. of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany for technical support regarding the primary histological examination and the preparation of the histological specimens, respectively. The Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany and the Department of Dermatology, Zealand University Hospital, University of Copenhagen, Roskilde, Denmark are health care units of the European Reference Network for Rare and Complex Skin Diseases (ERN Skin).
Funding Information:
This work was partially funded by a research grant to Christos C. Zouboulis from the German Federal Ministry of Education and Research (BMBF) [Project 0313660 ‘Investigation of gene expression in apocrine glands of patients with acne inversa (hidradenitis suppurativa)’] and Unilever R & D, Port Sunlight, Birmingham, UK.
Publisher Copyright:
© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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, HIF1α 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.
AB - 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, HIF1α 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.
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U2 - 10.1111/jdv.16147
DO - 10.1111/jdv.16147
M3 - Article
C2 - 31838778
AN - SCOPUS:85078843998
SN - 0926-9959
VL - 34
SP - 846
EP - 861
JO - Journal of the European Academy of Dermatology and Venereology
JF - Journal of the European Academy of Dermatology and Venereology
IS - 4
ER -