Mycobacterium bovis Bacillus Calmette–Guérin suppresses inflammatory Th2 responses by inducing functional alteration of TSLP-activated dendritic cells

Allergic diseases such as atopic dermatitis and asthma develop as a consequence of dysregulated Th2 responses. Recently, it has been demonstrated that interaction between dendritic cells (DCs) and thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine, is essential for evoking Th2 responses in allergy. In this study, we investigated whether Mycobacterium bovis Bacillus Calmette-Guerin (BCG), a strong Th1 response-inducing adjuvant, can alter the function of DCs activated by TSLP (TSLP- DCs). We demonstrated that BCG redirects TSLP-DCs away from inducing inflammatory Th2 cells that produce IL-4, IL-5, IL-13 and tumor necrosis factor (TNF)-a and toward regulatory Th1 cells that produce IFN-g and IL-10. We also demonstrated that this functional alteration of TSLP-DCs by BCG depended on both production of IL-12 from DCs and down-regulation of OX40 ligand, a member of the TNF family, on DCs. These findings suggest that BCG might be a useful adjuvant for the treatment of allergic diseases that are triggered by TSLP.