Hanadi Abid

NKT Cells in the Induced Sputum of Severe Asthmatics

To determine whether there was a specific inflammatory process in severe asthmatics, the phenotypic characteristics of induced sputum immune cells were analysed among patients with severe asthma. Twenty-two induced sputa (10 severe asthmatics) were studied. Flow cytometric analysis was performed using immune cells of the sputum and monoclonal antibodies to CD3, CD4, CD8, CD56, CD25, and TCRγδ. The number of NKT (CD3+CD56+) cells was significantly higher in the sputum of severe asthmatics compared with mild asthmatic and healthy control groups (P < .05). CD8+CD56+ cells were the predominant subtype of the increased NKT cells in severe asthmatics. CD3+CD56+Vα24+, TCRγδ+ CD56+, and CD4+CD25+ T cells were significantly increased in severe asthmatic patients. These results suggest that the immunopathogenesis of severe asthmatics vary between severe and mild asthmatics, and that CD8+CD56+ NKT cells may play an important role in the immunopathogenesis of severe asthma.

The impact of vitamin D deficiency on immune T cells in asthmatic children: a case-control study

Background Vitamin D exerts profound effects on both adaptive and innate immune functions involved in the development and course of autoimmune and inflammatory diseases. As the incidence of vitamin D insufficiency is surprisingly high in the general population, experimental studies have started to investigate whether vitamin D levels (measured as serum 25 hydroxy vitamin D-25[OH]D) are correlated with immune cells and clinical parameters. Purpose The aim of the present research was to investigate serum vitamin D status in a case-control study in children with asthma and to study associations between vitamin D levels and certain immunological parameters. Materials and methods A case control study of thirty-nine children with clinically controlled asthma was enrolled to assess the relationship between serum vitamin D concentrations and disease activity. Vitamin D was assayed with a radioimmunoassay kit. We evaluated the relationship between vitamin D concentrations and forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and the FEV1/FVC ratio. Correlations between inflammatory mediators, Th1, Th2, Th17, and regulatory T cells (Treg) and vitamin D were investigated. Results Only 15.38% of our asthmatic children had a sufficient serum 25(OH)D (≥30 ng/mL) whereas 80% of healthy children expressed sufficient levels. Deficient values of vitamin D (<20 ng/mL) were observed in 17 (43.59%) asthmatic patients (14.40 ± 3.30 ng/mL; P = 0.0001). Deficiency was not observed in controls. Th1/Th2 ratio was significantly correlated to 25(OH) D level (r = 0.698; P = 0.0001). A significant negative correlation was observed between serum interleukin-17 and vitamin D levels in young asthmatics (r = −0.617; P = 0.001). A significant correlation was observed between CD25+Foxp3+ Treg cells and vitamin D values in asthmatics (r = 0.368; P = 0.021). Conclusion Even in a southern Mediterranean country, hypovitaminosis D is frequent in children with asthma. Our findings suggest that vitamin D is an important promoter of T cell regulation in vivo in young asthmatics.

Transcriptional characteristics of CD4 T cells in young asthmatic children: RORC and FOXP3 axis.

Background Asthma is a chronic inflammatory disorder, hypothetically caused by autoreactive Th2 cells, whereas Th1 and regulatory T cells may confer protection. The development of Th subpopulations is dependent on the expression of lineage-specific transcription factors. Purpose This study aimed to assess the balance of CD4+ T cell populations in asthmatic children. Methods Peripheral blood mononuclear cells (PBMC) mRNA expression was assessed in 30 asthmatic children (18 patients with mild asthma and 12 with moderate asthma). Real-time polymerase chain reaction (RT-PCR) quantified TBX21, GATA-3, RORC, FOXP3, and EBI3 mRNA expression. Intracellular cytokine expression of IL-2, IL-4, IL-10, and IFN-γ in CD4+ T cells in asthmatic children was measured by flow cytometry. IL-6 and IL-17 cytokines were assessed in serum by enzyme-linked immunosorbent assay (ELISA). Results A significant increase was found in the percentage of CD4+ and CD8+ T cell-producing IL-4, IL-6, and IL-17. A decreased percentage of CD4+ producing IFN-γ in asthmatic children was found. Expression of GATA-3 (Th2), retinoid-related orphan receptor C (RORC) (Th17), and EBI3 were increased in asthmatic patients compared to healthy controls. Expression of FOXP3 (Treg) and TBX21 (Th1) were decreased (P < 0.0001 and P < 0.0001) in asthmatic children. Analysis of transcription factor ratios revealed an increase in the RORC/FOXP3 (P = 0.0001), and a significant decrease of TBX21/GATA-3 (P = 0.0001) ratios in patients with asthma. Conclusion Young asthmatics were characterized by increased IL-4 production and low IFN-γ synthesis. The increased serum IL-17 and IL-6 levels sustained an inflammatory environment in young asthmatics. The results indicate that FOXP3 and RORC mRNA expression could be associated with the sustained inflammatory process, transduced by low immune tolerance by Treg cells. The TBX21/GATA-3 and RORC/FOXP3 ratios dysregulation in asthmatics is consistent with the plasticity existing between Th1, Th17, and Treg cells during inflammation.

NOD2 is highly expressed in Behçet disease with pulmonary manifestations

BackgroundExcessive Th1 cells and TLRs functions are involved in the pathogenesis of Behcets disease (BD) in response to bacterial antigens. NOD2, an intracellular pathogen recognition sensor, modulates innate defence to muropeptides derived from various bacterial species. To further define a role for NOD2 in BD, we analysed NOD2 transcriptional responses in BAL-MNC from BD patients with pulmonary manifestations.MethodsWe analysed NOD1, NOD2, T-bet and TLRs mRNA expression with real-time polymerase chain-reaction in BAL cells obtained from 23 BD patients with pulmonary manifestations and their matched controls.ResultsWe found that NOD2 mRNA expression was highly up-regulated in BAL cells from BD and sarcoidosis patients compared to healthy control group (P = 0.001). In BD patients, significant correlation was found between NOD2 and T-bet mRNA expression (r = 0.602; P = 0.0009). In BAL from BD patients, NOD2 and T-bet mRNA expression were significantly correlated with BAL-lymphocytes (r = 0.485, P = 0.010; r = 0684, P = 0.0001 respectively). NOD2 in BD was also correlated with TLR 2(r = 0.444; P = 0.021) and TLR 4 (r = 0.574; P = 0.001) mRNA expression.ConclusionOur results indicate that BAL-MNC from BD patients expressed NOD2 as a result of lung inflammation. TLRs and NOD2 synergize for the induction of proinflammatory cytokines. BAL inflammatory cells showed an increased Th1 situation as indicated by increased T-bet mRNA expression.