Dataset Information

Wnt-activating human skin organoid model of atopic dermatitis induced by Staphylococcus aureus and its protective effects by Cutibacterium acnes.

ABSTRACT: A recently developed human PSC-derived skin organoid model has opened up new avenues for studying skin development, diseases, and regeneration. The current model has limitations since the generated organoids are enclosed, circular aggregates with an inside-out morphology with unintended off-target development of cartilage. Here, we first demonstrated that Wnt signaling activation resulted in larger organoids without off-target cartilage. We optimized further using an air-liquid interface (ALI) culture method to recapitulate structural features representative of human skin tissue. Finally, we used the ALI-skin organoid platform to model atopic dermatitis by Staphylococcus aureus (SA) colonization and infection. SA infection led to a disrupted skin barrier and increased production of epidermal- and dermal-derived inflammatory cytokines. Additionally, we found that pre-treatment with Cutibacterium acnes had a protective effect on SA-infected organoids. Thus, this ALI-skin organoid platform may be a useful tool for modeling human skin diseases and evaluating the efficacy of novel therapeutics.

SUBMITTER: Jung SY

PROVIDER: S-EPMC9526179 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Wnt-activating human skin organoid model of atopic dermatitis induced by <i>Staphylococcus aureus</i> and its protective effects by <i>Cutibacterium acnes</i>.

Jung Song-Yi SY You Hyun Ju HJ Kim Min-Ji MJ Ko GwangPyo G Lee Seunghee S Kang Kyung-Sun KS

iScience 20220916 10

A recently developed human PSC-derived skin organoid model has opened up new avenues for studying skin development, diseases, and regeneration. The current model has limitations since the generated organoids are enclosed, circular aggregates with an inside-out morphology with unintended off-target development of cartilage. Here, we first demonstrated that Wnt signaling activation resulted in larger organoids without off-target cartilage. We optimized further using an air-liquid interface (ALI) c ...[more]

PMID: 36193049

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Project description:Cutibacterium acnes is a human skin-resident bacterium. Although C. acnes maintains skin health by inhibiting invasion from pathogens like Staphylococcus aureus, it also contributes to several diseases, including acne. Studies suggest that differences in genetic background may explain the diverse phenotypes of C. acnes strains. In this study, we investigated the effects of C. acnes strains on the Caenorhabditis elegans life span and observed that some strains shortened the life span, whereas other strains, such as strain HL110PA4, did not alter it. Next, we assessed the effects of C. acnes HL110PA4 on host resistance against S. aureus. The survival time of C. acnes HL110PA4-fed wild-type animals was significantly longer than that of Escherichia coli OP50 control bacterium-fed worms upon infection with S. aureus. Although the survival times of worms harboring mutations at the daf-16/FoxO and skn-1/Nrf2 loci were similar to those of wild-type worms after S. aureus infection, administration of C. acnes failed to improve survival times of tir-1/SARM1, nsy-1/mitogen-activated protein kinase kinase kinase (MAPKKK), sek-1/mitogen-activated protein kinase kinase (MAPKK), and pmk-1/p38 mitogen-activated protein kinase (MAPK) mutants. These results suggest that the TIR-1 and p38 MAPK pathways are involved in conferring host resistance against S. aureus in a C. acnes-mediated manner. IMPORTANCE Cutibacterium acnes is one of the most common bacterial species residing on the human skin. Although the pathogenic properties of C. acnes, such as its association with acne vulgaris, have been widely described, its beneficial aspects have not been well characterized. Our study classifies C. acnes strains based on its pathogenic potential toward the model host C. elegans and reveals that the life span of C. elegans worms fed on C. acnes was consistent with the clinical association of C. acnes ribotypes with acne or nonacne. Furthermore, nonpathogenic C. acnes confers host resistance against the opportunistic pathogen Staphylococcus aureus. Our study provides insights into the impact of C. acnes on the host immune system and its potential roles in the ecosystem of skin microbiota.

Dataset Information

Wnt-activating human skin organoid model of atopic dermatitis induced by Staphylococcus aureus and its protective effects by Cutibacterium acnes.

Publications

Wnt-activating human skin organoid model of atopic dermatitis induced by <i>Staphylococcus aureus</i> and its protective effects by <i>Cutibacterium acnes</i>.

Similar Datasets

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