The single nucleotide polymorphism <scp><i>CRTh2</i></scp> rs533116 is associated with allergic asthma and increased expression of <scp>CRT</scp>h2

Campos-Alberto, Eduardo; MacLean, E.; Davidson, Courtney; Palikhe, Nami Shrestha; Storie, Jessica; Tse, Chi; Brenner, Darren M.; Mayers, Irvin; Vliagoftis, Harissios; El-Sohemy, Ahmed; Cameron, Lisa

doi:10.1111/all.12003

Cited by 20 publications

(19 citation statements)

References 37 publications

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“…We optimized the cycle number to be within the exponential phase of amplification. PCR with 2 µL of DNase/RNase free water (Sigma) instead of cDNA was run as a negative control and cDNA from human Th2 cells (CRTh2 + /CD4 + T cells differentiated in vitro by culturing in Th2-polarizing conditions [44] ) was used as a positive control for DP2. The PCR products were analyzed by 1% agarose gel electrophoresis with ethidium bromide staining and confirmed by sequencing (DNA Core Services Lab, University of Alberta).…”

Section: Methodsmentioning

confidence: 99%

Expression of DP2 (CRTh2), a Prostaglandin D2 Receptor, in Human Mast Cells

et al. 2014

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PGD2 has long been implicated in allergic diseases. Recent cloning of a second PGD2 receptor, DP2 (also known as CRTh2), led to a greater understanding of the physiological and pathophysiological implications of PGD2. PGD2 signaling through DP1 and DP2 mediates different and often opposite effects in many cell types of the immune system. Although mast cells (MC) are the largest source of PGD2 in the body, there is little information about their potential expression of DP2 and its functional significance. In this study, we show that tissue MC in human nasal polyps express DP2 protein, and that human MC lines and primary cultured human MC express mRNA as well as protein of DP2. By immunohistochemistry, we detected that 34% of MC in human nasal polyps expressed DP2. In addition, flow cytometry showed that 87% of the LAD2 human MC line and 98% of primary cultured human MC contained intracellular DP2. However, we could not detect surface expression of DP2 on human MC by single cell analysis using imaging flow cytometry. Blocking of endogenous PGD2 production with aspirin did not induce surface expression of DP2 in human MC. Two DP2 selective agonists, DK-PGD2 and 15R-15-methyl PGD2 induced dose-dependent intracellular calcium mobilization that was abrogated by pertussis toxin, but not by three DP2 selective antagonists. MC mediator release including degranulation was not affected by DP2 selective agonists. Thus, human MC express DP2 intracellularly rather than on their surface, and the function of DP2 in human MC is different than in other immune cells such as Th2 cells, eosinophils and basophils where it is expressed on the cell surface and induces Th2 cytokine and/or granule associated mediator release. Further studies to elucidate the role of intracellular DP2 in human MC may expand our understanding of this molecule and provide novel therapeutic opportunities.

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Section: Methodsmentioning

confidence: 99%

Expression of DP2 (CRTh2), a Prostaglandin D2 Receptor, in Human Mast Cells

et al. 2014

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“…In vivo studies using CRTh2 −/− mice or CRTh2 antagonists showed that this receptor mediates cellular and physiologic responses in models of allergic disease . In humans, CRTh2 + CD3 + T cells are increased in allergic tissues and we and others showed that blood levels of CRTh2 + CD4 + T cells are higher in subjects with allergic airways disease compared with non‐allergic controls . Furthermore, the level of CRTh2 has been reported to be upregulated on eosinophils in eosinophilic esophagitis .…”

Section: Introductionmentioning

confidence: 72%

Elevated levels of circulating CD4⁺CRTh2⁺ T cells characterize severe asthma

Palikhe

Laratta

Nahirney

et al. 2016

Clin Experimental Allergy

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“…Contrary to expectation, the frequency of A carrier (GA + AA genotypes), which shows lower expression of the CRTH2 gene, was higher in patients with GD (Table 4), and there was no association of this SNP with the intractability of GD. This may be because in patients with GD, who show a higher proportion of Th17 cells [12], the expression level of CRTH2, which induces Th2 cytokine expression [30], and the suppression of Th17 cells by Th2 cells may be too weak to affect the GD intractability [16,18]. In the case of the rs634681 SNP, the frequencies of the T allele and the T allele carrier were higher in patients with mild HD than those with severe HD (Table 5).…”

Section: Discussionmentioning

confidence: 99%

“…PGD 2 -CRTH2 signaling induces chemotaxis and expression of Th2 cytokines and is important for allergic inflammation such as asthma [27][28][29]. The single nucleotide polymorphisms (SNPs) in the CRTH2 gene, rs533116, rs545659, rs634681 and rs11571288, have been associated with asthma and allergic sensitization and the functions of these polymorphisms were shown in Table 1 [30][31][32][33][34][35]. Therefore, these CRTH2 SNPs may be associated with chemotaxis of Th2 cells to thyroid gland and induction of Th2 differentiation through IL-4 and IL-13 signaling.…”

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confidence: 99%

Association of the polymorphisms in Th2 chemotaxis-related genes with the development and prognosis of autoimmune thyroid diseases

et al. 2018

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The prognosis of autoimmune thyroid disease (AITD) is difficult to predict. Th2 cells suppress the differentiation of Th1 and Th17 cells, which are associated with the prognosis of AITD. However, there are few reports as to whether Th2 chemotaxis-related genes, such as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), IL-25, TARC/CCL17 (Thymus and activation regulated chemokine/chemokine ligand 17) or STAT6 (Signal transducer and activator of transcription 6), affect the pathology of and/or susceptibility to AITD. Therefore, in this study, we genotyped functional SNPs in these genes to clarify the association of the genetic differences of genes related to Th2 differentiation and chemotaxis with the development and the prognosis of AITDs. The frequencies of the AA genotype of the CRTH2 rs545659 SNP and the CC genotype and the C allele of the CRTH2 rs634681 SNP were higher in patients with severe HD than in patients with mild HD. The frequency of the CC genotype in the TARC rs223828 SNP was higher in patients with intractable GD than in patients with GD in remission. In conclusion, the CRTH2 rs545659 and rs634681 SNPs were associated with the severity of HD, and the TARC/CCL17 rs223828 SNP was associated with the intractability of GD.

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The single nucleotide polymorphism CRTh2 rs533116 is associated with allergic asthma and increased expression of CRTh2

Abstract: These findings show an association between CRTh2 rs533116 and allergic asthma and suggest this may be mediated by elevated expression of CRTh2, leading to higher numbers of circulating eosinophils and Th2 cytokine production.

Cited by 20 publications

References 37 publications

Expression of DP2 (CRTh2), a Prostaglandin D2 Receptor, in Human Mast Cells

Expression of DP2 (CRTh2), a Prostaglandin D2 Receptor, in Human Mast Cells

Elevated levels of circulating CD4⁺CRTh2⁺ T cells characterize severe asthma

Association of the polymorphisms in Th2 chemotaxis-related genes with the development and prognosis of autoimmune thyroid diseases

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The single nucleotide polymorphism CRTh2 rs533116 is associated with allergic asthma and increased expression of CRTh2

Abstract: These findings show an association between CRTh2 rs533116 and allergic asthma and suggest this may be mediated by elevated expression of CRTh2, leading to higher numbers of circulating eosinophils and Th2 cytokine production.

Cited by 20 publications

References 37 publications

Expression of DP2 (CRTh2), a Prostaglandin D2 Receptor, in Human Mast Cells

Expression of DP2 (CRTh2), a Prostaglandin D2 Receptor, in Human Mast Cells

Elevated levels of circulating CD4+CRTh2+ T cells characterize severe asthma

Association of the polymorphisms in Th2 chemotaxis-related genes with the development and prognosis of autoimmune thyroid diseases

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Elevated levels of circulating CD4⁺CRTh2⁺ T cells characterize severe asthma