PT - JOURNAL ARTICLE AU - Renga, Giorgia AU - Oikonomou, Vasilis AU - Moretti, Silvia AU - Stincardini, Claudia AU - Bellet, Marina M AU - Pariano, Marilena AU - Bartoli, Andrea AU - Brancorsini, Stefano AU - Mosci, Paolo AU - Finocchi, Andrea AU - Rossi, Paolo AU - Costantini, Claudio AU - Garaci, Enrico AU - Goldstein, Allan L AU - Romani, Luigina TI - Thymosin β4 promotes autophagy and repair via HIF-1α stabilization in chronic granulomatous disease AID - 10.26508/lsa.201900432 DP - 2019 Dec 01 TA - Life Science Alliance PG - e201900432 VI - 2 IP - 6 4099 - http://www.life-science-alliance.org/content/2/6/e201900432.short 4100 - http://www.life-science-alliance.org/content/2/6/e201900432.full SO - Life Sci. Alliance2019 Dec 01; 2 AB - Chronic granulomatous disease (CGD) is a genetic disorder of the NADPH oxidase characterized by increased susceptibility to infections and hyperinflammation associated with defective autophagy and increased inflammasome activation. Herein, we demonstrate that thymosin β4 (Tβ4), a g-actin sequestering peptide with multiple and diverse intracellular and extracellular activities affecting inflammation, wound healing, fibrosis, and tissue regeneration, promoted in human and murine cells noncanonical autophagy, a form of autophagy associated with phagocytosis and limited inflammation via the death-associated protein kinase 1. We further show that the hypoxia inducible factor-1 (HIF-1)α was underexpressed in CGD but normalized by Tβ4 to promote autophagy and up-regulate genes involved in mucosal barrier protection. Accordingly, inflammation and granuloma formation were impaired and survival increased in CGD mice with colitis or aspergillosis upon Tβ4 treatment or HIF-1α stabilization. Thus, the promotion of endogenous pathways of inflammation resolution through HIF-1α stabilization is druggable in CGD by Tβ4.