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HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling.
Loh, Zhixuan; Simpson, Jennifer; Ullah, Ashik; Zhang, Vivian; Gan, Wan J; Lynch, Jason P; Werder, Rhiannon B; Sikder, Al Amin; Lane, Katie; Sim, Choon Boon; Porrello, Enzo; Mazzone, Stuart B; Sly, Peter D; Steptoe, Raymond J; Spann, Kirsten M; Sukkar, Maria B; Upham, John W; Phipps, Simon.
Afiliación
  • Loh Z; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
  • Simpson J; Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia.
  • Ullah A; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
  • Zhang V; QIMR Berghofer Medical Research Institute, Queensland, Australia.
  • Gan WJ; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
  • Lynch JP; QIMR Berghofer Medical Research Institute, Queensland, Australia.
  • Werder RB; QIMR Berghofer Medical Research Institute, Queensland, Australia.
  • Sikder AA; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
  • Lane K; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
  • Sim CB; QIMR Berghofer Medical Research Institute, Queensland, Australia.
  • Porrello E; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
  • Mazzone SB; QIMR Berghofer Medical Research Institute, Queensland, Australia.
  • Sly PD; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
  • Steptoe RJ; QIMR Berghofer Medical Research Institute, Queensland, Australia.
  • Spann KM; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
  • Sukkar MB; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Australia.
  • Upham JW; Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Australia.
  • Phipps S; School of Biomedical Sciences, The University of Queensland, Queensland, Australia.
PLoS Pathog ; 16(7): e1008651, 2020 07.
Article en En | MEDLINE | ID: mdl-32658914
Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant tissue remodelling, as observed in asthma. Severe respiratory viral infections in infancy predispose to later asthma, however, the processes that mediate tissue damage-induced type-2 inflammation and the origins of airway remodelling remain ill-defined. Here, using a preclinical mouse model of viral bronchiolitis, we find that increased epithelial and mesenchymal high-mobility group box 1 (HMGB1) expression is associated with increased numbers of IL-13-producing type-2 innate lymphoid cell (ILC2s) and the expansion of the airway smooth muscle (ASM) layer. Anti-HMGB1 ablated lung ILC2 numbers and ASM growth in vivo, and inhibited ILC2-mediated ASM cell proliferation in a co-culture model. Furthermore, we identified that HMGB1/RAGE (receptor for advanced glycation endproducts) signalling mediates an ILC2-intrinsic IL-13 auto-amplification loop. In summary, therapeutic targeting of the HMGB1/RAGE signalling axis may act as a novel asthma preventative by dampening ILC2-mediated type-2 inflammation and associated ASM remodelling.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos / Proteína HMGB1 / Remodelación de las Vías Aéreas (Respiratorias) / Inflamación / Músculo Liso Límite: Animals Idioma: En Revista: PLoS Pathog Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos / Proteína HMGB1 / Remodelación de las Vías Aéreas (Respiratorias) / Inflamación / Músculo Liso Límite: Animals Idioma: En Revista: PLoS Pathog Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos