The mRNA level of Charcot–Leyden crystal protein/galectin-10 is a marker for CRTH2 activation in human whole blood<i>in vitro</i>

Lin, Tai-An; Kourteva, Galina; Hilton, Holly; Liu, Hongli; Tare, Nadine S.; Carvajal, Valerie; Hang, Julie S.; Wei, Xin; Renzetti, Louis M.

doi:10.3109/1354750x.2010.511266

Cited by 11 publications

(6 citation statements)

References 36 publications

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“…Among the genes showing ≥3-fold differences in expression between IgG4-RD patients and controls, we selected CLC because of its clinical association with type I hypersensitivity such as bronchial asthma [ 23 , 24 ]. Furthermore, CLC protein has been reported to be a marker of chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2), a prostaglandin D2 receptor [ 25 ], and CLC expression has been observed in the cytoplasm of CD4 + CD25 + Tregs, with little expression in CD4 + CD25 - T cells [ 26 ]. We found that the level of CLC mRNA was significantly lower in IgG4-RD patients than in controls ( Fig 1 ), despite the serum IgE concentrations being higher in IgG4-RD patients ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease

et al. 2015

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BackgroundIgG4-related disease (IgG4-RD) is a new clinical entity of unknown etiology characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. Although aberrancies in acquired immune system functions, including increases in Th2 and Treg cytokines observed in patients with IgG4-RD, its true etiology remains unclear. To investigate the pathogenesis of IgG4-RD, this study compared the expression of genes related to innate immunity in patients with IgG4-RD and healthy controls.Materials and MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from patients with IgG4-RD before and after steroid therapy and from healthy controls. Total RNA was extracted and DNA microarray analysis was performed in two IgG4-RD patients to screen for genes showing changes in expression. Candidate genes were validated by real-time RT-PCR in 27 patients with IgG4-RD and 13 healthy controls.ResultsDNA microarray analysis identified 21 genes that showed a greater than 3-fold difference in expression between IgG4-RD patients and healthy controls and 30 genes that showed a greater than 3-fold change in IgG4-RD patients following steroid therapy. Candidate genes related to innate immunity, including those encoding Charcot–Leyden crystal protein (CLC), membrane-spanning 4-domain subfamily A member 3 (MS4A3), defensin alpha (DEFA) 3 and 4, and interleukin-8 receptors (IL8R), were validated by real-time RT-PCR. Expression of all genes was significantly lower in IgG4-RD patients than in healthy controls. Steroid therapy significantly increased the expression of DEFA3, DEFA4 and MS4A3, but had no effect on the expression of CLC, IL8RA and IL8RB.ConclusionsThe expression of genes related to allergy or innate immunity, including CLC, MS4A3, DEFA3, DEFA4, IL8RA and IL8RB, was lower in PBMCs from patients with IgG4-RD than from healthy controls. Although there is the limitation in the number of patients applied in DNA microarray, impaired expression of genes related to innate immunity may be involved in the pathogenesis of IgG4-RD as well as in abnormalities of acquired immunity.

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Section: Discussionmentioning

confidence: 99%

Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease

et al. 2015

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“…19 Overexpression of CLC/Gal-10 mRNA was noted in the peripheral blood of patients with aspirin-induced asthma, and mRNA levels of CLC/Gal-10 were also shown to be a marker of CRTH2 activation. 20,21 Genetic variation in CLC/Gal-10 was found to be associated with allergic rhinitis, and patients with seasonal allergic rhinitis were found to have elevated levels of CLC/Gal-10 present in nasal lavage fluid during allergy season. 22,23 Analysis of protein expression patterns in gut biopsy samples from patients with celiac disease found a positive correlation between CLC/Gal-10 levels and tissue damage, and a recent study showed that higher levels of CLC/Gal-10 mRNA distinguished children with eosinophilic esophagitis from control children.…”

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confidence: 99%

Charcot-Leyden crystal protein/galectin-10 interacts with cationic ribonucleases and is required for eosinophil granulogenesis

Grozdanović

Doyle

Liu

et al. 2020

Journal of Allergy and Clinical Immunology

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Charcot-Leyden Crystal Protein/Galectin-10 Interacts with Cationic Ribonucleases and is Required for Eosinophil Granulogenesis EDN CLC/Gal-10 CD63 CLC/Gal-10 CLC/Gal-10 colocalizes with the secondary granule's tetraspanin (CD63) and with EDN (RNase2) during eosinophil degranulation CD34 IL-5Rα IL-5Rα Siglec-8 CCR3 CLC/Gal-10 Secondary granules EDN (RNase2), ECP (RNase3), MBP-1, EPX, cytokines, etc.

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“…This gene is expressed in a variety of tissues and body fluids and is a known marker for allergic inflammation in asthma and allergic rhinitis. However, the role and function of CLC is not entirely understood[37].…”

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Changes in the human transcriptome upon vitamin D supplementation

Pasing

Fenton²,

Jorde

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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Vitamin D is hydroxylated in the liver and kidneys to its active form, which can bind to the vitamin D receptor (VDR). The VDR is present in a wide variety of different cells types and tissues and acts as a transcription factor. Although activation of the VDR is estimated to regulate expression of up to 5% of the human genome, our study is the first analysing gene expression after supplementation in more than 10 subjects. Subjects of a randomized controlled trial (RCT) received either vitamin D (n=47) in a weekly dose of 20,000 IU or placebo (n=47) for a period of three to five years. For this study, blood samples for preparation of RNA were drawn from the subjects and mRNA gene expression in blood was determined using microarray analysis. The two study groups were similar regarding gender, age, BMI and duration of supplementation, whereas the mean serum 25-hydroxyvitamin D (25(OH)D) level as expected was significantly higher in the vitamin D group (119 versus 63nmol/L). When analysing all subjects, nearly no significant differences in gene expression between the two groups were found. However, when analysing men and women separately, significant effects on gene expression were observed for women. Furthermore, when only including subjects with the highest and lowest serum 25(OH)D levels, additional vitamin D regulated genes were disclosed. Thus, a total of 99 genes (p≤0.05, log2 fold change ≥|0.2|) were found to be regulated, of which 72 have not been published before as influenced by vitamin D. These genes were particularly involved in the interleukin signaling pathway, oxidative stress response, apoptosis signaling pathway and gonadotropin releasing hormone receptor pathway. Thus, our results open the possibility for many future studies.

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The mRNA level of Charcot–Leyden crystal protein/galectin-10 is a marker for CRTH2 activation in human whole bloodin vitro

Cited by 11 publications

References 36 publications

Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease

Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease

Charcot-Leyden crystal protein/galectin-10 interacts with cationic ribonucleases and is required for eosinophil granulogenesis

Changes in the human transcriptome upon vitamin D supplementation

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