| Literature DB >> 32240121 |
Cindy Orvain1,2, Yea-Lih Lin3, Francette Jean-Louis1,2, Hakim Hocini1,2, Barbara Hersant4,5,6, Yamina Bennasser3, Nicolas Ortonne5,6,7, Claire Hotz4,5,6,8, Pierre Wolkenstein4,5,6,8, Michele Boniotto1,6, Pascaline Tisserand1,2, Cécile Lefebvre1,2, Jean-Daniel Lelièvre1,2,5,6,9, Monsef Benkirane3, Philippe Pasero3, Yves Lévy1,2,5,6,9, Sophie Hüe1,2,5,6,10.
Abstract
Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease. HS appears to be a primary abnormality in the pilosebaceous-apocrine unit. In this work, we characterized hair follicle stem cells (HFSCs) isolated from HS patients and more precisely the outer root sheath cells (ORSCs). We showed that hair follicle cells from HS patients had an increased number of proliferating progenitor cells and lost quiescent stem cells. Remarkably, we also showed that the progression of replication forks was altered in ORSCs from hair follicles of HS patients, leading to activation of the ATR/CHK1 pathway. These alterations were associated with an increased number of micronuclei and with the presence of cytoplasmic ssDNA, leading to the activation of the IFI16/STING pathway and the production of type I IFNs. This mechanistic analysis of the etiology of HS in the HFSC compartment establishes a formal link between genetic predisposition and skin inflammation observed in HS.Entities:
Keywords: Adult stem cells; Cellular immune response; Dermatology; Immunology
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Year: 2020 PMID： 32240121 PMCID： PMC7324185 DOI： 10.1172/JCI131180
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808