Cis -acting lnc-Cxcl2 restrains neutrophil-mediated lung inflammation by inhibiting epithelial cell CXCL2 expression in virus infection

Significance Epithelial cell–mediated chemokine production and subsequent neutrophil recruitment are important for pathogen clearance, which, however, are also closely related to severe inflammatory tissue damage during lung infection, especially influenza virus infection and the current pandemic coronavirus infection. Certain regulation and underlying mechanisms of chemokine expression in epithelial cells remain largely unknown. Here, by identifying the mouse long noncoding RNA lnc-Cxcl2 and human lnc-CXCL2-4-1 in virus-infected lung epithelial cells, we demonstrated a self-protecting mechanism in host lung epithelial cells for restraining viral infection–induced lung inflammation through feedback-suppressing chemokine expression. These findings provide better understandings of chemokine regulation and epithelial cell function during lung viral infection and will benefit the treatment of related lung infectious diseases.