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Hematopoietic Stem Cells response to allergic peritonitis

ABSTRACT: In our previous work we substantiated the ability of the Fgd5-mCherry mice to tag hematopoietic stem cells (HSCs) during immune response (Bujanover et al., 2018). While most of the research is focused on viral-bacterial models mediated by a Th1 response less has been investigated on Th2 mediated hypersensitivity. Our current experimental model of allergic peritonitis seeks to understand the effect of a Th2 mediated immune response utilizing our transgenic Fgd5-mCherry mice. Our results showed no significant change in quantity of HSCs and their immediate progenitors in the bone-marrow post treatment. Furthermore, transplant experiments showed no significant change in the long term multipotent ability of HSCs vs. control. Examining the cell cycle state of HSCs, quiescence is an essential property for stemness, we find no evidence of proliferation. We continued to sort and bulk RNAseq HSCs after allergic peritonitis showing relatively small changes in expression profile. Taken together, this data suggests no prominent response of HSCs to our Th2-mediated hypersensitivity model.

ORGANISM(S): Mus musculus

PROVIDER: GSE133282 | GEO | 2020/04/30

REPOSITORIES: GEO

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Project description:Background: The prevalence of individuals allergic to latex, exhibiting cross-hypersensitivity with plant-derived food has been frequently reported as the so-called latex-fruit syndrome. Nonetheless, molecular mechanisms underlying allergy to latex and/or fruit are poorly understood. Objective: The aims of this study were to identify candidate genes that may be associated with the pathogenesis of allergy to latex and /or vegetable food, and to assess if similar molecular pathways are involved in both types of hypersensitivity. Methods: DNA microarray analysis was performed to screen the molecular profiles of peripheral blood mononuclear cells isolated from patients with allergy to latex, to fruit, or with latex-fruit syndrome, and from control healthy subjects. Results: Gene expression profiling identified an overlapping dataset of genes commonly regulated in all the atopic patients enrolled in this study, suggesting that similar molecular mechanisms are involved in the pathogenesis of allergy to the fruit and /or latex. Several regulators of the innate and acquired immunity reported to polarize the immunological response towards a Th2-mediated immune response were overexpressed in patients. Furthermore, evidences suggested that T regulatory cell expression might be defective in allergic patients, as a consequence of a dysregulation of some inflammatory cytokines. Finally, several transcription factors that may be responsible for the Th1/Th2 imbalance were modulated in allergic patients. Conclusion and clinical implications: This study identified relevant genes that may help to elucidate the molecular mechanisms underlying allergic disease. Knowledges of critical targets, along with transcription factors regulating gene activity may facilitate the development of new therapies. Experiment Overall Design: This study aimed at the understanding of the molecular pathways involved in allergy to latex and fruit. As latex and vegetable food allergens cross-react, it could be hypothesized that similar pathways are involved in both types of hypersensitivity. Experiment Overall Design: For this purpose, patients allergic to latex (n=6), allergic to vegetable food (n=5), or suffering from latex-fruit syndrome (n=6) were enrolled from the Unit of Allergy of the Gemelli Hospital of Rome. Moreover, 4 healthy volunteers were added to this study. Five ml of blood were harvested from each individual, and PBMCs were isolated on ficoll gradient. Following sample preparation (as recommended by the manufacturer), each sample was hybridized on Affymetrix human focus array. Data were processed with Affymetrix MAS 5.0 software and averaged intensity of signals from biological replicates were calculated for further analysis. Experiment Overall Design: The CEL files for this study were lost in a computer crash.

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Hematopoietic Stem Cells response to allergic peritonitis

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