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Background Respiratory allergies rely on a defect of IL-10-secreting regulatory CD4+T-cells (IL-10-Tregs) leading to excessive Th2-biased immune responses to allergens. According to clinical data, the restoration of allergen-specific IL-10-Tregs is required to control respiratory allergies and cure patients. The discovery of mechanisms involved in the generation of IL-10-Tregs will thus help to provide effective treatments. We previously demonstrated that dendritic cells (DCs) expressing high levels of the glucocorticoid-induced leucine zipper protein (GILZ) generate antigen-specific IL-10-Tregs. Objective We suspect a defective expression of GILZ in the DCs of respiratory allergic patients and speculate that increasing its expression might restore immune tolerance against allergens through the induction of IL-10-Tregs. Methods We assessed GILZ expression in blood DCs of patients and healthy nonallergic donors by qPCR. We compared the ability of patients' DCs to induce allergen-specific IL-10-Tregs before and after an in vivo up-regulation of GILZ expression by steroid administration, steroids being inducers of GILZ. Results We report lower levels of GILZ in DCs of respiratory allergic patients that return to normal levels after steroid administration. We show that patients' DCs with increased levels of GILZ generate allergen-specific IL-10-Tregs again. We further confirm unequivocally that GILZ is required in patients' DCs to activate these IL-10-Tregs. Conclusion This proof of concept study shows that the re-establishment of GILZ expression in patients' DCs to normal levels restores their capacity to activate allergen-specific IL-10-Tregs. We thus highlight the up-regulation of GILZ in DCs as a new interventional approach to restore the immune tolerance to allergens.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a rare variant of severe asthma resulting from hypersensitivity to Aspergillus fumigatus (Asp f) present in the airways. Aims of the study: We analyzed the expression of a panel of six chemokine receptors (CCR3, CCR4, CCR8, CCR5, CXCR3 and CXCR4) on total blood CD4+ T cells and Asp f-specific-T cells in ABPA patients. We hypothesized that chemokine receptor pattern on T cells differs between ABPA patients, non-ABPA allergic asthmatics sensitized to Dermatophagoides pteronyssinus (Der p) or Phleum pratense (Phl p) and healthy controls. Methods: We used the fluorescent dye PKH26, a membrane bound marker, to identify accumulated proliferating (cell-sorted PKH26low) CD4+ T cells in response to allergens (Asp f, Der p, Phl p) or recall antigens (PPD and TT). Chemokine receptor expression was analyzed by flow cytometry on proliferating CD3+ CD4+ PKH26low cells. Results: Stimulation of CD4+ T cells with the relevant allergen resulted in different patterns of chemokine receptor expression in ABPA and non-ABPA allergic asthmatics. Upon Asp f exposure, proliferating CD4+ T cells from ABPA patients down-regulated the expression of CCR4 and CXCR3 while CCR4 and CXCR3 were up-regulated in allergen-specific T cells from non-ABPA allergic asthmatics. Considering each group of patients, the pattern of chemokine receptors expressed on proliferating allergen-specific CD4+ T cells was similar to that expressed by recall antigen-specific T cells. Conclusions: The down-regulation of CCR4 and CXCR3 after allergen exposure in Asp f-specific T cells seems to be a characteristic feature of ABPA patients and requires further evaluation.