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Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells.
Bangert, Christine; Alkon, Natalia; Chennareddy, Sumanth; Arnoldner, Tamara; Levine, Jasmine P; Pilz, Magdalena; Medjimorec, Marco A; Ruggiero, John; Cohenour, Emry R; Jonak, Constanze; Damsky, William; Griss, Johannes; Brunner, Patrick M.
Afiliación
  • Bangert C; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Alkon N; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Chennareddy S; Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
  • Arnoldner T; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Levine JP; Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
  • Pilz M; New York Medical College, Valhalla, NY, USA.
  • Medjimorec MA; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Ruggiero J; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Cohenour ER; Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
  • Jonak C; Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
  • Damsky W; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Griss J; Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
  • Brunner PM; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Nat Commun ; 15(1): 2839, 2024 Apr 02.
Article en En | MEDLINE | ID: mdl-38565563
ABSTRACT
Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients. Histopathological features distinct from AD suggest a drug effect, but exact underlying mechanisms remain unknown. We profiled punch biopsies from dupilumab-associated head and neck dermatitis (DAHND) by using single-cell RNA sequencing and compared data with untreated AD and healthy control skin. We show that dupilumab treatment was accompanied by normalization of IL-4/IL-13 downstream activity markers such as CCL13, CCL17, CCL18 and CCL26. By contrast, we found strong increases in type 22-associated markers (IL22, AHR) especially in oligoclonally expanded T cells, accompanied by enhanced keratinocyte activation and IL-22 receptor upregulation. Taken together, we demonstrate that dupilumab effectively dampens conventional type 2 inflammation in DAHND lesions, with concomitant hyperactivation of IL22-associated responses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dermatitis Atópica / Anticuerpos Monoclonales Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dermatitis Atópica / Anticuerpos Monoclonales Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido