Dectin-2–Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation
In: Journal of Investigative Dermatology, Jg. 139 (2019-03-01), S. 702-711
Online
unknown
Zugriff:
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.
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Dectin-2–Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation
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Autor/in / Beteiligte Person: | Tada, Hiroyuki ; Kyo, Yoshika ; Yokoyama, Rin ; Masaki, Airi ; Takagi, Naoyuki ; Imai, Yoshimichi ; Miura, Takayuki ; Kitai, Yuki ; Yamaguchi, Natsuki ; Iwakura, Yoichiro ; Kawakami, Kazuyoshi ; Tachi, Masahiro ; Kanno, Emi ; Sato, Noriko ; Ishii, Keiko ; Saijo, Shinobu ; Kawamura, Kotone ; Tanno, Hiromasa ; Yamaguchi, Kenji |
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Zeitschrift: | Journal of Investigative Dermatology, Jg. 139 (2019-03-01), S. 702-711 |
Veröffentlichung: | Elsevier BV, 2019 |
Medientyp: | unknown |
ISSN: | 0022-202X (print) |
DOI: | 10.1016/j.jid.2018.10.015 |
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