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

First Author  Miura T Year  2019
Journal  J Invest Dermatol Volume  139
Issue  3 Pages  702-711
PubMed ID  30393083 Mgi Jnum  J:310205
Mgi Id  MGI:6756461 Doi  10.1016/j.jid.2018.10.015
Citation  Miura T, et al. (2019) Dectin-2-Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation. J Invest Dermatol 139(3):702-711
abstractText  Dendritic cell-associated C-type lectin-2 (i.e., dectin-2) recognizes fungal polysaccharides, including alpha-mannan. Dectin-2-mediated recognition of fungi, such as Candida albicans, leads to NF-kappaB 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 alpha-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 alpha-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 alpha-mannan delayed wound closure in wild-type mice, and these responses were canceled in dectin-2-knockout mice. Furthermore, mice administered alpha-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 alpha-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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