Interferon regulatory factor 5 involves immune responses through regulation of ly6c expression

Abstract

Abstract Chronic obstructive pulmonary disease (COPD) is characterized by impaired lung function, prolonged airflow obstruction. COPD is mainly induced by long-tern exposure to toxic agents such as particles from cigarette smoke (CS). Interferon regulatory factor 5 (IRF5) is a key transcription factor related to many inflammatory diseases. IRF5 has been involved in polarizing macrophages and recruiting neutrophiles during various conditions. The purpose of this study was to assess immune responsiveness of IRF5 in lung disease. We generated mice deficient in the Irf5 gene (Irf5−/− mice). IRF5 expression was detected in lung and spleen of wild type (WT) mice but not in Irf5−/− mice. After whole-body inhalation exposure of CS, WT and Irf5−/− mice were decreased body wight and showed changed pressure-volume loop. In addition, the number of immune cells in the bronchoalveolar lavage fluid (BALF) was remarkably increased both in WT and in Irf5−/− mice after smoking compared to the non-smoking groups of WT and Irf5−/− mice. The CD11b+F4/80-CCR2+Ly6C+ cells were significantly increased in the BALF of smoking-exposed Irf5−/− mice compared to in that of smoking-exposed WT mice. Also, fecal microbiota analysis showed differences in bacterial abundances between WT smoking and Irf5−/− smoking mice. Taken together, our present findings suggest smoking-exposed Irf5−/− mice showed higher level of Ly6C expression in immune cells of the BALF and differential bacterial abundances in the feces. Further studies are required to elucidate IRF5-regulating Ly6C expression and determine potential therapeutic applications for COPD.