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CXCL12+ dermal fibroblasts promote neutrophil recruitment and host defense by recognition of IL-17.
Cavagnero, Kellen J; Li, Fengwu; Dokoshi, Tatsuya; Nakatsuji, Teruaki; O'Neill, Alan M; Aguilera, Carlos; Liu, Edward; Shia, Michael; Osuoji, Olive; Hata, Tissa; Gallo, Richard L.
Afiliação
  • Cavagnero KJ; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Li F; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Dokoshi T; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Nakatsuji T; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • O'Neill AM; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Aguilera C; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Liu E; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Shia M; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Osuoji O; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Hata T; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
  • Gallo RL; Department of Dermatology, University of California, San Diego. La Jolla, CA, USA.
J Exp Med ; 221(4)2024 Apr 01.
Article em En | MEDLINE | ID: mdl-38393304
ABSTRACT
The skin provides an essential barrier for host defense through rapid action of multiple resident and recruited cell types, but the complex communication network governing these processes is incompletely understood. To define these cell-cell interactions more clearly, we performed an unbiased network analysis of mouse skin during invasive S. aureus infection and revealed a dominant role for CXCL12+ fibroblast subsets in neutrophil communication. These subsets predominantly reside in the reticular dermis, express adipocyte lineage markers, detect IL-17 and TNFα, and promote robust neutrophil recruitment through NFKBIZ-dependent release of CXCR2 ligands and CXCL12. Targeted deletion of Il17ra in mouse fibroblasts resulted in greatly reduced neutrophil recruitment and increased infection by S. aureus. Analogous human CXCL12+ fibroblast subsets abundantly express neutrophil chemotactic factors in psoriatic skin that are subsequently decreased upon therapeutic targeting of IL-17. These findings show that CXCL12+ dermal immune acting fibroblast subsets play a critical role in cutaneous neutrophil recruitment and host defense.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Staphylococcus aureus / Interleucina-17 Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Staphylococcus aureus / Interleucina-17 Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article