Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response

Tanno, Hiromasa; Kawakami, Kazuyoshi; Emi, Kazuyuki; Suzuki, Atsushi; Takagi, Naoyuki; Yamamoto, Hiromitsu; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro

doi:10.1111/wrr.12588

Cited by 43 publications

(30 citation statements)

References 40 publications

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“…In addition, our study showed that administration of a-mannan accelerated neutrophil elastase synthesis and that treatment with a neutrophil elastase inhibitor led to improvement of the delayed wound healing caused by a-mannan. NETs contain a high concentration of neutrophil elastase (Brinkmann et al, 2004), which causes degradation of tissue matrix and delay of wound healing (Herrick et al, 1997;Takagi et al, 2017;Tanno et al, 2017). Neutrophil elastase is not only one of the NET components but also acts as an inducer of NET formation (Papayannopoulos et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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

Miura

Kawakami

Emi

et al. 2019

Journal of Investigative Dermatology

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Dendritic cell-associated C-type lectin-2 (i.e., dectin-2) recognizes fungal polysaccharides, including a-mannan. Dectin-2emediated recognition of fungi, such as Candida albicans, leads to NF-kB 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 a-mannan affected the wound healing process. Full-thickness wounds were created on the backs of wild type C57BL/6 and dectin-2edeficient 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 a-mannan. The percent wound closure and re-epithelialization was significantly accelerated in dectin-2eknockout mice compared with wild-type mice on days 3 and 5 after wounding. In contrast, administration of a-mannan delayed wound closure in wild-type mice, and these responses were canceled in dectin-2eknockout mice. Furthermore, mice administered a-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 a-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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Section: Discussionmentioning

confidence: 99%

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

Miura

Kawakami

Emi

et al. 2019

Journal of Investigative Dermatology

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“…The lack of lymphocytes was found to impair the inflammatory response during injury with a consequence of impaired angiogenesis and an increase in metalloproteinase levels [ 24 ]. In addition, several subsets of T-cell [ 25 ], B-cell [ 26 ], Natural Killer (NK)T-cell [ 27 ] and regulatory T-cells [ 28 ] contribute to wound healing ( Table 1 ) ( Figure 1 ).…”

Section: The Dynamic Phases Of Normal Wound Healingmentioning

confidence: 99%

Mechanistic Actions of microRNAs in Diabetic Wound Healing

Petković

Sørensen

Leal

et al. 2020

Cells

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Wound healing is a complex biological process that is impaired under diabetes conditions. Chronic non-healing wounds in diabetes are some of the most expensive healthcare expenditures worldwide. Early diagnosis and efficacious treatment strategies are needed. microRNAs (miRNAs), a class of 18–25 nucleotide long RNAs, are important regulatory molecules involved in gene expression regulation and in the repression of translation, controlling protein expression in health and disease. Recently, miRNAs have emerged as critical players in impaired wound healing and could be targets for potential therapies for non-healing wounds. Here, we review and discuss the mechanistic background of miRNA actions in chronic wounds that can shed the light on their utilization as specific wound healing biomarkers.

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“…Delayed scar formation may be caused by the regulation of cytokine expression (IL-1B, IL-23, IL-17A) released by Vy4 T cells activated through the T cell receptor (TCR) pathway [233]. Invariant natural killer T (iNKT) cells, which have antigenic features of both T cells and NK cells, regulate neutrophil apoptosis by the expression of IFN-γ, which limits the damage caused by the release of neutrophil elastase, which in turn accelerates the wound healing process [234]. The wound healing process is disturbed in neoplastic diseases, where delayed regeneration actions have been observed at every wound healing stage, and monocyte and T cell infiltration were found to be significantly less in cancer cases than in normal controls, which was associated with a local limitation of neovascularization and collagen synthesis [235].…”

Section: Wound Healingmentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response

Cited by 43 publications

References 40 publications

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

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

Mechanistic Actions of microRNAs in Diabetic Wound Healing

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

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