Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa.
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
17
07
2019
accepted:
20
11
2019
pubmed:
16
12
2019
medline:
30
1
2021
entrez:
16
12
2019
Statut:
ppublish
Résumé
The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting. Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. 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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting.
OBJECTIVE
OBJECTIVE
Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments.
METHODS
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
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
CONCLUSIONS
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.
Banques de données
GENBANK
['NM_002421', 'NM_002965', 'NM_005557', 'NM_004994', 'NM_002974', 'NM_006919', 'NM_005416', 'NM_001062', 'NM_003278', 'NM_005621', 'NM_182633', 'NM_005555', 'NM_000669', 'NM_000999', 'NM_001928', 'NM_198460', 'NM_004942', 'NM_006829', 'NM_005276', 'NM_004004', 'NM_002638', 'NM_032959', 'NM_001001479', 'NM_173086', 'NM_002964', 'NM_176823', 'NM_024771', 'NM_000150', 'NR_003287', 'NM_017781', 'NM_001033045', 'NR_024207', 'NM_005554', 'AK000470', 'NM_001060', 'NM_172002', 'NM_015603', 'NM_004262', 'NM_144613', 'NM_020682', 'NR_026802', 'NM_001040125', 'NM_207373', 'NM_181877', 'NM_012269', 'NM_001104595', 'AK056486', 'NM_001145418', 'NM_032251', 'NM_001444', 'NM_022904', 'NM_001008540', 'NM_002963', 'NM_001042422', 'NM_006235', 'NM_020939', 'NM_000215', 'NM_031910', 'NM_021181', 'NM_003485', 'NM_001164741', 'NM_006288', 'NM_003474', 'NM_001127663']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
846-861Subventions
Organisme : German Federal Ministry of Education and Research (BMBF)
Organisme : Unilever R & D, Port Sunlight, Birmingham, UK
Informations de 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.
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