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Immunological cell type characterization and Th1-Th17 cytokine production in a mouse model of Gaucher disease.

ABSTRACT: Gaucher disease is a lysosomal storage disease resulting from insufficient acid ?-glucosidase (glucocerebrosidase, GCase, EC 4.2.1.25) activity and the resultant accumulation of glucosylceramide. Macrophage (M?) lineage cells are thought to be the major disease effectors because of their secretion of numerous cytokines and chemokines that influence other poorly defined immunological cell populations. Increases in several such populations were identified in a Gba1 mouse model (D409V/null; 9V/null) of Gaucher disease including antigen presenting cells (APCs), i.e., M?, dendritic cells (DCs), neutrophils (PMNs), and CD4(+) T cells. FACS analyses showed increases in these cell types in 9V/null liver, spleen lung, and bone marrow. T-cells or APCs enhanced activations were evident by positivity of CD40L, CD69, as well as CD40, CD80, CD86, and MHCII on the respective cells. M?, and, unexpectedly, DCs, PMNs, and T cells, from 9V/null mice showed excess glucosylceramides as potential bases for activation of APCs and T cells to induce Th1 (IFN?, IL12, TNF?,) and Th17 (IL17A/F) cytokine production. These data imply that excess glucosylceramides in these cells are pivotal for activation of APCs and T cell induction of Th1 and Th17 responses and PMN recruitment in multiple organs of this model of Gaucher disease.

SUBMITTER: Pandey MK

PROVIDER: S-EPMC3382074 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Immunological cell type characterization and Th1-Th17 cytokine production in a mouse model of Gaucher disease.

Pandey Manoj Kumar MK Rani Reena R Zhang Wujuan W Setchell Kenneth K Grabowski Gregory A GA

Molecular genetics and metabolism 20120430 3

Gaucher disease is a lysosomal storage disease resulting from insufficient acid β-glucosidase (glucocerebrosidase, GCase, EC 4.2.1.25) activity and the resultant accumulation of glucosylceramide. Macrophage (Mϕ) lineage cells are thought to be the major disease effectors because of their secretion of numerous cytokines and chemokines that influence other poorly defined immunological cell populations. Increases in several such populations were identified in a Gba1 mouse model (D409V/null; 9V/null ...[more]

PMID: 22595426

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Project description:Asthma is a chronic inflammatory disease with no definite treatment and more research is needed to overcome this condition. The aim of this study was to investigate the effect of the extract of Zataria multiflora (Z. multiflora) as a medicinal plant on cytokine genes expression in an experimental mouse model of asthma. Adult mice were randomly divided into the following groups: control (C), untreated asthma (A), asthmatic groups treated with dexamethasone (D) and Z. multiflora extract (200, 400, and 800 μg/mL; Z1, Z2, and Z3, respectively), (for groups C, A, and D n = 5 and for groups Z1, Z2, and Z3 n = 6). For induction of the mouse model of asthma, animals were sensitized with intraperitoneal injection and inhalation of ovalbumin (OVA). The number of T helper (Th) subtype cells (using flow cytometry) and the levels of IFN-γ, FOXP3, IL-4, TGF-β, IL-17 gene expression (by real time PCR) were assessed in mice splenocytes. The observed changes in spleen cells of group A compared to group C were increased number of Th2 and Th17 cells, enhancement of gene expression of IL-4, IL-17, and TGF-β (p < 0.001 for all cases), reduction of Th1 cells and Th1/Th2 ratio (p < 0.001 for both cases) and decrease in gene expression of IFN-γ, FOXP3 and IFN-γ/IL-4 ratio (p < 0.01 for IFN-γ and p < 0.001 for other cases). The observed changes in spleen cells of treated compared to untreated A group were enhancement of Treg cells and Th1/Th2 ratio (p < 0.001 for both cases), increase in IFN-γ (p < 0.05) and FOXP3 (p < 0.001) gene expression and IFN-γ/IL-4 ratio (p < 0.01) as well as reduction of Th2 and Th17 cells (p < 0.01 to p < 0.001), decrease gene expression of IL-4, IL-17, and TGF-β (p < 0.05 to p < 0.001). The findings showed that the extract of Z. multiflora decreased pro-inflammatory cytokines in asthma (IL-4 and IL-17 and TGF-β) but increased anti-inflammatory cytokines (IFN-γ) gene expression and the number of Treg (FOXP3) in splenocytes of asthmatic mice which may indicate the specific therapeutic effect of the plant extract in allergy, autoimmunity, and infectious diseases via potentiating Th1 and suppressing Th2 and Th17 cells.

Dataset Information

Immunological cell type characterization and Th1-Th17 cytokine production in a mouse model of Gaucher disease.

Publications

Immunological cell type characterization and Th1-Th17 cytokine production in a mouse model of Gaucher disease.

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