MicroRNA-22 Inhibits Histone Deacetylase 4 to Promote T Helper-17 Cell-Dependent Emphysema

Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (T(H)17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-κB. MiR-22-deficient mice, but not wild-type, showed attenuated T(H)17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and T(H)17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and T(H)17 responses.