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High expression of miR-222-3p in children with Mycoplasma pneumoniae pneumonia. OBJECTIVES: Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia in children. However, its mechanism of pathogenesis is not fully understood, and microRNAs might play a role. This study aimed to explore the microRNA-222-3p (miR-222-3p) expression and its possible role in children with M.pneumoniae pneumonia (MPP). METHODS: Thirty-six children with MPP and twenty-seven age-matched controls from Children's Hospital of Soochow University were enrolled in this study. MiR-222-3p and cluster of differentiation 4 (CD4) mRNA were detected using real-time PCR in children's peripheral blood plasma samples. THP-1 cells and mice were stimulated with M.pneumoniae lipid-associated membrane proteins(LAMPs). RESULTS: Children with MPP had significantly higher levels of miR-222-3p and lower levels of CD4 in peripheral blood plasma (P <  0.05). Additionally, Sixteen children with MPP complicated with pleural effusion had higher miR-222-3p levels than those without pleural effusion. MiR-222-3p or CD4 in THP-1 cells increased or decreased, respectively, in a dose dependent manner after LAMP stimulation. In LAMP-stimulated mice massive inflammatory cells infiltrates surrounded the bronchioles, and miR-222-3p increased in the bronchoalveolar lavage fluid. In conclusion, miR-222-3p was highly expressed in children with MPP, especially those with pleural effusion. CONCLUSION: Small sample studies showed that M.pneumoniae or its LAMPs could increase miR-222-3p and decrease CD4 in macrophages,both in vitro and vivo.Thus, miR-222-3p might be an MPP biomarker for the diagnosis and prognosis.