Chitinase 3-like 1 plays a pivotal role in airway response of RSV infection via regulating DC functional transition.

ABSTRACT

BACKGROUND: Dendritic cells (DCs) contribute to immune imbalance and airway hyperresponsiveness (AHR) induced by respiratory syncytial virus (RSV). The aim of present study was to explore the mechanism of RSV regulating naive T cell differentiation through DCs. METHODS: We generated a Lentivirus shRNA expression vector to knock down CHI3L1 in mouse lungs and bone marrow-derived dendritic cells (BMDCs). Then we investigated the effect of CHI3L1 knockdown on MAPK/ERK pathway, PI3K/AKT pathway, mature DCs represented by molecular markers, naive T cell differentiation and related cytokine expression in vitro and in vivo models of RSV. RESULTS: RSV elevated CHI3L1 expression in lung DCs and BMDCs. Knockdown of CHI3L1 impeded RSV-induced activation of MAPK/ERK and PI3K/AKT signaling pathways, attenuated CD86 and OX40L expression in mature DCs, reduced the proportion of Th2 and Th17 cells, and increased the proportion of Treg cells. In addition, by blocking CHI3L1, RSV-infected mice shown relief of airway resistance, the downregulation of Th2/Th17 like cytokines IL-4, IL-13 and IL-17 levels, and the upregulation of IL-10. CONCLUSION: Our data show that CHI3L1 promotes RSV induced immune imbalance and airway hyperresponsiveness by regulating the functional transformation of DCs.