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Deletion of S100a8 and S100a9 Enhances Skin Hyperplasia and Promotes the Th17 Response in Imiquimod-Induced Psoriasis.
Defrêne, Joan; Berrazouane, Sofiane; Esparza, Nayeli; Pagé, Nathalie; Côté, Marie-France; Gobeil, Stéphane; Aoudjit, Fawzi; Tessier, Philippe A.
Afiliação
  • Defrêne J; Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada.
  • Berrazouane S; Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada.
  • Esparza N; Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada.
  • Pagé N; Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada.
  • Côté MF; Axe Endocrinologie et Néphrologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada.
  • Gobeil S; Axe Endocrinologie et Néphrologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada.
  • Aoudjit F; Département de Médecine Moléculaire, Faculté de Médecine, Université Laval, Quebec City, Quebec G1V 0A6, Canada; and.
  • Tessier PA; Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada.
J Immunol ; 206(3): 505-514, 2021 02 01.
Article em En | MEDLINE | ID: mdl-33361205
High concentrations of the damage-associated molecular patterns S100A8 and S100A9 are found in skin and serum from patients suffering from psoriasis, an IL-17-related disease. Notably, although the expression of these proteins correlates with psoriatic disease severity, the exact function of S100A8 and S100A9 in psoriasis pathogenesis remains unclear. In this study, we investigated the role of S100A8 and S100A9 in psoriasis-associated skin hyperplasia and immune responses using S100a8-/- and S100a9-/- mice in an imiquimod-induced model of psoriasis. We found that S100a8-/- and S100a9-/- psoriatic mice exhibit worsened clinical symptoms relative to wild-type mice and increased expression of S100A9 and S100A8 proteins in keratinocytes, respectively. In addition, the loss of S100A8 enhances proliferation of keratinocytes and disrupts keratinocyte differentiation. We further detected elevated production of IL-17A and -F from CD4+ T cells in the absence of S100A8 and S100A9, as well as increased infiltration of neutrophils in the skin. In addition, treatment with anti-IL-17A and -F was found to reduce psoriasis symptoms and skin hyperplasia in S100a8-/- and S100a9-/- mice. These data suggest that S100A8 and S100A9 regulate psoriasis by inhibiting production of IL-17A and -F, thereby, to our knowledge, providing new insights into their biological functions.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Psoríase / Pele / Interleucina-17 / Calgranulina A / Calgranulina B / Células Th17 Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Psoríase / Pele / Interleucina-17 / Calgranulina A / Calgranulina B / Células Th17 Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article