Pular para o conteúdo
Merck
  • Hair follicle stem cell replication stress drives IFI16/STING-dependent inflammation in hidradenitis suppurativa.

Hair follicle stem cell replication stress drives IFI16/STING-dependent inflammation in hidradenitis suppurativa.

The Journal of clinical investigation (2020-04-03)
Cindy Orvain, Yea-Lih Lin, Francette Jean-Louis, Hakim Hocini, Barbara Hersant, Yamina Bennasser, Nicolas Ortonne, Claire Hotz, Pierre Wolkenstein, Michele Boniotto, Pascaline Tisserand, Cécile Lefebvre, Jean-Daniel Lelièvre, Monsef Benkirane, Philippe Pasero, Yves Lévy, Sophie Hüe
RESUMO

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.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
MISSION® esiRNA, targeting human IFI16