miR-23∼27∼24 clusters restrict Th2 immunity and associated immunopathology during airway allergic reaction (HYP2P.335)

Abstract

MiRNAs (miRNAs) are important regulators in T cell differentiation and function. Here we show miR-23~27~24 clusters play a pivotal role in controlling type II immunity. Specifically, under Th2 polarizing condition, T cells with overexpression of miR-23~27~24 clusters exhibited reduced IL-4 secretion whereas T cells devoid of miR-23~27~24 clusters produced elevated amounts of IL-4. Further mechanistic studies revealed miR-24 and miR-27 could repress Gata3, a key regulator of Th2 cell differentiation through an indirect and a direct manner, respectively. Finally, by using an OVA-induced asthma model, we have shown that mice with T cell-specific ablation of miR-23~27~24 clusters developed a more severe airway inflammation characterized by increased IL-4 secretion, lung eosinophil infiltration, mucin production and serum IgE levels. Taken together, our studies identify a miRNA family with important biological function particularly in controlling Th2 immunity and suggest that a tight regulation of this miRNA family is required to maintain optimal effector T cell function and to prevent aberrant immune responses.