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CD301b+ Macrophages Are Essential for Effective Skin Wound Healing.

ABSTRACT: Regeneration of skin's barrier function after injury requires temporally coordinated cellular interactions between multiple cell types. Macrophages are essential inflammatory cells in skin wound regeneration. These cells switch their phenotype from inflammatory in the early regenerative stages to anti-inflammatory in the midstages of healing to coordinate skin repair. However, little is known about how different subsets of anti-inflammatory macrophages contribute to skin wound healing. Here, we characterize midstage macrophages (CD45(+)/CD11b(+)/F4-80(+)) and identify two major populations: CD206(+)/CD301b(+) and CD206(+)/CD301b(-). The numbers of CD206(+)/CD301b(+) macrophages increased concomitantly with repair, when the anti-inflammatory phenotype switch occurs in midstage healing. Using diphtheria toxin-mediated depletion models in mice, we show that selective depletion of midstage CD301b-expressing macrophages phenocopied wound healing defects observed in mice where multiple myeloid lineages are depleted. Additionally, when FACS-isolated subpopulations of myeloid cells were transplanted into 3-day wounds of syngeneic mice, only CD206(+)/CD301b(+) macrophages significantly increased proliferation and fibroblast repopulation. These data show that the CD301b-expressing subpopulation of macrophages is critical for activation of reparative processes during the midstage of cutaneous repair.

SUBMITTER: Shook B

PROVIDER: S-EPMC5727894 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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CD301b+ Macrophages Are Essential for Effective Skin Wound Healing.

Shook Brett B Xiao Eric E Kumamoto Yosuke Y Iwasaki Akiko A Horsley Valerie V

The Journal of investigative dermatology 20160607 9

Regeneration of skin's barrier function after injury requires temporally coordinated cellular interactions between multiple cell types. Macrophages are essential inflammatory cells in skin wound regeneration. These cells switch their phenotype from inflammatory in the early regenerative stages to anti-inflammatory in the midstages of healing to coordinate skin repair. However, little is known about how different subsets of anti-inflammatory macrophages contribute to skin wound healing. Here, we ...[more]

PMID: 27287183

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Project description:BackgroundThe anti-inflammatory properties of the cannabinoid 2 receptor (CB2R) in injury and inflammatory diseases have been widely substantiated. Specifically, the anti-inflammatory effect of CB2R may be achieved by regulating macrophage polarisation. Several research findings suggested that the activation of CB2R could attenuate inflammation by reducing pro-inflammatory M1 macrophage polarisation and promoting anti-inflammatory M2 polarisation. However, considering CB2R inhibits fibrosis and M2 promotes fibrosis, that the activation of CB2R may lead to an increase in M2 macrophages seems contradictory. Therefore, we hypothesised that the activation of CB2R to attenuate inflammation is not achieved by up-regulating M2 macrophages.MethodsWe established an incised wound model using mouse skin and used this to evaluate the effect of CB2R agonists (JWH133 or GP1a) and an antagonist (AM630) on wound healing. At various post-injury intervals, we used western blot analysis, immunofluorescence staining, enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction assays to determine CB2R protein expression, M1/M2 macrophage infiltration, and the protein and gene expression of M1/M2-associated markers and cytokines in skin lesions.ResultsActivation of CB2R significantly reduced M1 macrophage infiltration and slightly increased M2 macrophage infiltration. Similarly, gene expression and protein levels of M1-associated markers and cytokines (interleukin [IL]-6, IL-12, CD86 and inducible nitric oxide synthase) were significantly down-regulated after CB2R agonist administration; in contrast, markers and cytokines were increased in the CB2R antagonist-treated group. Conversely, the administration of agonists slightly increased gene expression and protein levels of M2-associated markers and cytokines (IL-4, IL-10, CD206 and arginase-1 [Arg-1]); however, a statistical significance at most time points post-injury was not noted.ConclusionIn summary, our findings suggested that during incised skin wound healing in mice, increased levels of CB2R may affect inflammation by regulating M1 rather than M2 macrophage subtype polarisation. These results offer a novel understanding of the molecular mechanisms involved in the inhibition of inflammation by CBR2 that may lead to new treatments for cutaneous inflammation.

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CD301b+ Macrophages Are Essential for Effective Skin Wound Healing.

Publications

CD301b+ Macrophages Are Essential for Effective Skin Wound Healing.

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