Dataset Information

PH and Proton Sensor GPR65 Determine Susceptibility to Atopic Dermatitis.

ABSTRACT: pH sensing by GPR65 regulates various inflammatory conditions, but its role in skin remains unknown. In this study, we performed a phenome-wide association study and report that the T allele of GPR65-intronic single-nucleotide polymorphism rs8005161, which reduces GPR65 signaling, showed a significant association with atopic dermatitis, in addition to inflammatory bowel diseases and asthma, as previously reported. Consistent with this genetic association in humans, we show that deficiency of GPR65 in mice resulted in markedly exacerbated disease in the MC903 experimental model of atopic dermatitis. Deficiency of GPR65 also increased neutrophil migration in vitro. Moreover, GPR65 deficiency in mice resulted in higher expression of the inflammatory cytokine TNF-α by T cells. In humans, CD4⁺ T cells from rs8005161 heterozygous individuals expressed higher levels of TNF-α after PMA/ionomycin stimulation, particularly under pH 6 conditions. pH sensing by GPR65 appears to be important for regulating the pathogenesis of atopic dermatitis.

SUBMITTER: Xie L

PROVIDER: S-EPMC8674371 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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pH and Proton Sensor GPR65 Determine Susceptibility to Atopic Dermatitis.

Xie Liang L McKenzie Craig I CI Qu Xinyan X Mu Yan Y Wang Quanbo Q Bing Nan N Naidoo Karmella K Alam Md Jahangir MJ Yu Di D Gong Fang F Ang Caroline C Robert Remy R Marques Francine Z FZ Furlotte Nicholas N Hinds David D Gasser Olivier O Xavier Ramnik J RJ Mackay Charles R CR

Journal of immunology (Baltimore, Md. : 1950) 20210616 1

pH sensing by GPR65 regulates various inflammatory conditions, but its role in skin remains unknown. In this study, we performed a phenome-wide association study and report that the T allele of <i>GPR65</i>-intronic single-nucleotide polymorphism rs8005161, which reduces GPR65 signaling, showed a significant association with atopic dermatitis, in addition to inflammatory bowel diseases and asthma, as previously reported. Consistent with this genetic association in humans, we show that deficiency ...[more]

PMID: 34135065

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Project description:We characterized the population of Staphylococcus aureus from patients with atopic dermatitis (AD) in terms of (i) genetic diversity, (ii) presence and functionality of genes encoding important virulence factors: staphylococcal enterotoxins (sea, seb, sec, sed), toxic shock syndrome 1 toxin (tsst-1), and Panton-Valentine leukocidin (lukS/lukF-PV) by spa typing, PCR, drug resistance profile determination, and Western blot. We then subjected the studied population of S. aureus to photoinactivation based on a light-activated compound called rose bengal (RB) to verify photoinactivation as an approach to effectively kill toxin-producing S. aureus. We have obtained 43 different spa types that can be grouped into 12 clusters, indicating for the first-time clonal complex (CC) 7 as the most widespread. A total of 65% of the tested isolates had at least one gene encoding the tested virulence factor, but their distribution differed between the group of children and adults, and between patients with AD and the control group without atopy. We detected a 3.5% frequency of methicillin-resistant strains (MRSA) and no other multidrug resistance. Despite genetic diversity and production of various toxins, all isolates tested were effectively photoinactivated (bacterial cell viability reduction ≥ 3 log10 units) under safe conditions for the human keratinocyte cell line, which indicates that photoinactivation can be a good option in skin decolonization. IMPORTANCE Staphylococcus aureus massively colonizes the skin of patients with atopic dermatitis (AD). It is worth noting that the frequency of detection of multidrug-resistant S. aureus (MRSA) in AD patients is higher than the healthy population, which makes treatment much more difficult. Information about the specific genetic background of S. aureus accompanying and/or causing exacerbations of AD is of great importance from the point of view of epidemiological investigations and the development of possible treatment options.

Dataset Information

PH and Proton Sensor GPR65 Determine Susceptibility to Atopic Dermatitis.

Publications

pH and Proton Sensor GPR65 Determine Susceptibility to Atopic Dermatitis.

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