Enhanced glucocorticoid‐induced leucine zipper in dendritic cells induces allergen‐specific regulatory CD 4 + T ‐cells in respiratory allergies

Background Respiratory allergies rely on a defect of IL ‐10‐secreting regulatory CD 4 + T ‐cells ( IL ‐10‐ T regs ) leading to excessive T h2‐biased immune responses to allergens. According to clinical data, the restoration of allergen‐specific IL ‐10‐ T regs is required to control respiratory allergies and cure patients. The discovery of mechanisms involved in the generation of IL ‐10‐ T regs will thus help to provide effective treatments. We previously demonstrated that dendritic cells ( DC s) expressing high levels of the glucocorticoid‐induced leucine zipper protein ( GILZ ) generate antigen‐specific IL ‐10‐ T regs . Objective We suspect a defective expression of GILZ in the DC s of respiratory allergic patients and speculate that increasing its expression might restore immune tolerance against allergens through the induction of IL ‐10‐ T regs . Methods We assessed GILZ expression in blood DC s of patients and healthy nonallergic donors by qPCR . We compared the ability of patients' DC s to induce allergen‐specific IL ‐10‐ T regs 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 DC s of respiratory allergic patients that return to normal levels after steroid administration. We show that patients' DC s with increased levels of GILZ generate allergen‐specific IL ‐10‐ T regs again. We further confirm unequivocally that GILZ is required in patients' DC s to activate these IL ‐10‐ T regs . Conclusion This proof of concept study shows that the re‐establishment of GILZ expression in patients' DC s to normal levels restores their capacity to activate allergen‐specific IL ‐10‐ T regs . We thus highlight the up‐regulation of GILZ in DC s as a new interventional approach to restore the immune tolerance to allergens.