Dectin-2–Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation

Takayuki Miura, Kazuyoshi Kawakami, Emi Kanno, Hiromasa Tanno, Hiroyuki Tada, Noriko Sato, Airi Masaki, Rin Yokoyama, Kotone Kawamura, Yuki Kitai, Naoyuki Takagi, Kenji Yamaguchi, Natsuki Yamaguchi, Yoshika Kyo, Keiko Ishii, Yoshimichi Imai, Shinobu Saijo, Yoichiro Iwakura, Masahiro Tachi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Dendritic cell-associated C-type lectin-2 (i.e., dectin-2) recognizes fungal polysaccharides, including α-mannan. Dectin-2–mediated recognition of fungi, such as Candida albicans, leads to NF-κB activation, which induces production of inflammatory cytokines. However, the role of dectin-2 in skin wound healing remains unclear. In this study, we sought to determine how dectin-2 deficiency and the administration of α-mannan affected the wound healing process. Full-thickness wounds were created on the backs of wild type C57BL/6 and dectin-2–deficient mice. We analyzed wound closure, histological findings, and re-epithelialization. We also examined the neutrophilic inflammatory responses and neutrophil extracellular trap (NET)-osis at the wound sites after administration of α-mannan. The percent wound closure and re-epithelialization was significantly accelerated in dectin-2–knockout mice compared with wild-type mice on days 3 and 5 after wounding. In contrast, administration of α-mannan delayed wound closure in wild-type mice, and these responses were canceled in dectin-2–knockout mice. Furthermore, mice administered α-mannan, neutrophil infiltration was prolonged, and the expression of citrullinated histone, an indicator of NETosis, at the wound sites was accelerated. Administration of a neutrophil elastase inhibitor significantly improved the delayed wound healing caused by α-mannan. These results suggest that dectin-2 may have a deep impact on the skin wound healing process through regulation of neutrophilic responses.

Original languageEnglish
Pages (from-to)702-711
Number of pages10
JournalJournal of Investigative Dermatology
Volume139
Issue number3
DOIs
Publication statusPublished - 2019 Mar

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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