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Immunomodulatory effects of canine mesenchymal stem cells in an experimental atopic dermatitis model.

ABSTRACT: Mesenchymal stem cells (MSCs) have the potential to differentiate into multi-lineage cells, suggesting their future applicability in regenerative medicine and biotechnology. The immunomodulatory properties of MSCs make them a promising replacement therapy in various fields of animal research including in canine atopic dermatitis (AD), a skin disease with 10-15% prevalence. We investigated the immunomodulatory effects of MSCs in an experimental canine AD model induced by Dermatophagoides farinae extract ointment. Canine adipose tissue-derived MSCs (cAT-MSCs) were differentiated into mesodermal cell lineages at the third passage. Alterations in immunomodulatory factors in control, AD, and MSC-treated AD groups were evaluated using flow cytometric analysis, enzyme-linked immunosorbent assay, and quantitative reverse transcription PCR. In the MSC-treated AD group, the number of eosinophils decreased, and the number of regulatory T cells (Tregs) increased compared to those in the AD group. In addition, the immunoglobulin E (IgE) and prostaglandin E₂ levels were reduced in the MSC-treated AD group compared to those in the AD group. Furthermore, the filaggrin, vascular endothelial growth factor, and interleukin-5 gene expression levels were relatively higher in the MSC-treated AD group than in the AD group, however, not significantly. cAT-MSCs exerted immunomodulatory effects in an AD canine model via a rebalancing of type-1 and -2 T helper cells that correlated with increased levels of Tregs, IgE, and various cytokines.

SUBMITTER: Kang SJ

PROVIDER: S-EPMC10390254 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Immunomodulatory effects of canine mesenchymal stem cells in an experimental atopic dermatitis model.

Kang Seok-Jin SJ Gu Na-Yeon NY Byeon Jeong Su JS Hyun Bang-Hun BH Lee Jienny J Yang Dong-Kun DK

Frontiers in veterinary science 20230713

Mesenchymal stem cells (MSCs) have the potential to differentiate into multi-lineage cells, suggesting their future applicability in regenerative medicine and biotechnology. The immunomodulatory properties of MSCs make them a promising replacement therapy in various fields of animal research including in canine atopic dermatitis (AD), a skin disease with 10-15% prevalence. We investigated the immunomodulatory effects of MSCs in an experimental canine AD model induced by <i>Dermatophagoides farin ...[more]

PMID: 37529178

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Project description:There is no established protocol for the development of an experimental canine atopic dermatitis model in laboratory beagles. This study aimed to establish an experimental model that mimics spontaneous canine atopic dermatitis (CAD) clinically, immunologically, and microbiologically, by repeated epicutaneous applications of mite antigens and to describe the entire process including sensitization and provocation in detail for reproducibility. Six intact male laboratory beagle dogs aged 14 months were included in this study. During the sensitization and provocation phase, the house dust mite (HDM) paste consisted of Dermatophagoides farinae (Der f ) and mineral oil, which was applied focally to the 10 × 10 cm area of the right groin as evenly as possible. Further, 120 mg of Der f was applied to each dog twice a week for 12 weeks during the sensitization phase and 25 mg and 120 mg was applied to each dog for the first 2 weeks and subsequent 2 weeks, respectively, during the provocation phase. Thereafter, the applied area was covered with a dressing. Skin lesions including erythema, hyperpigmentation, excoriation, and lichenification were induced and exacerbated gradually through the experimental time course in all six dogs. The canine atopic dermatitis extent and severity index (CADESI) score and transepidermal water loss (TEWL) significantly increased after sensitization and provocation. IL-13 and IL-31 levels increased significantly after provocation as a result of the activation of the T helper-2 (Th2) response. On the contrary, the IL-10 levels decreased significantly after sensitization, which suggested a suppression of Tregs activity. After the completion of provocation, skin microbiome analysis showed that Firmicutes was the most abundant phylum, which indicated bacterial dysbiosis. This study demonstrated that epicutaneous application of HDM in beagle dogs resulted in the elevation of serum HDM-specific IgE levels and clinical atopic scores, a high TEWL, and microbiome dysbiosis resembling spontaneous CAD. These results suggest that this tailored protocol of epicutaneous exposure to Der f may provide support for the development of the experimental CAD model in laboratory beagles.

Project description:BackgroundAtopic dermatitis (AD) is one of the most common cutaneous inflammatory and pruritic diseases in dogs. Considering its multifactorial nature, AD can be a challenging disease to manage, and the therapeutic strategy must often be multimodal. In recent years, research has been moving toward the use of natural products which have beneficial effects on inflammation and itching, and no side effects. Cannabinoid receptors have been demonstrated to be expressed in healthy and diseased skin; therefore, one of the potential alternative therapeutic targets for investigating AD is the endocannabinoid system (ECS).ObjectiveTo immunohistochemically investigate the expression of the cannabinoid receptor type 2 (CB2R), and the cannabinoid-related receptors G protein-coupled receptor 55 (GPR55), transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) in mast cells (MCs), macrophages, dendritic cells (DCs), T cells, and neutrophils of the skin of dogs with AD.AnimalsSamples of skin tissues were collected from eight dogs with AD (AD-dogs).Materials and methodsThe immunofluorescent stained cryosections of the skins of 8 dogs with AD having antibodies against CB2R, GPR55, TRPV1, TRPA1 were semiquantitatively evaluated. The inflammatory cells were identified using antibodies against tryptase (mast cells), ionized calcium binding adaptor molecule 1 (IBA1) (macrophages/DCs), CD3 (T cells), and calprotectin (neutrophils). The proportions of MCs, macrophages/DCs, T cells, and neutrophils expressing CB2R, GPR55, TRPV1 and TRPA1 were evaluated.ResultsThe cells of the inflammatory infiltrate showed immunoreactivity (IR) for all or for some of the cannabinoid and cannabinoid-related receptors studied. In particular, MCs and macrophages/DCs showed CB2R-, GPR55-, TRPA1-, and TRPV1-IR; T cells showed CB2R-, GPR55- and TRPA1-IR, and neutrophils expressed GPR55-IR. Co-localization studies indicated that CB2R-IR was co-expressed with TRPV1-, TRPA1-, and GPR55-IR in different cellular elements of the dermis of the AD-dogs.Conclusions and clinical importanceCannabinoid receptor 2, and cannabinoid-related receptors GPR55, TRPV1 and TRPA1 were widely expressed in the inflammatory infiltrate of the AD-dogs. Based on the present findings, the ECS could be considered to be a potential therapeutic target for dogs with AD, and may mitigate itch and inflammation.

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Immunomodulatory effects of canine mesenchymal stem cells in an experimental atopic dermatitis model.

Publications

Immunomodulatory effects of canine mesenchymal stem cells in an experimental atopic dermatitis model.

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