CD38 gene-modified dendritic cells inhibit murine asthma development by increasing IL-12 production and promoting Th1 cell differentiation

Abstract

Predominant T helper (Th)2 and impaired Th1 cell polarization has a crucial role in the development of asthma. Cluster of differentiation (CD)38 is associated with the increased release of interleukin (IL)12 from dendritic cells (DCs) and DCinduced Th1 cell polarization. However, whether CD38 expression affects DC function in asthma development remains unknown. In the current study, adenoviruses were constructed containing the murine CD38 gene. Overexpression of CD38 protein level in DCs induced from bonemarrow derived DCs (BMDCs) by recombinant mouse granulocyte macrophage colonystimulating factor and IL4 was achieved through 24 h adenovirus infection. The results demonstrated that BMDCs with CD38 overexpression exhibited no phenotypic change; however, following stimulation with lipopolysaccharide (LPS), maturation and IL12 secretion were increased. In addition, CD38overexpressing BMDCs stimulated with LPS exhibited more effective Th1 cell differentiation. Mice that were administered CD38overexpressing BMDCs exhibited milder symptoms of asthma. Furthermore, decreased IL4, IL5 and IL13 levels were detected in bronchoalveolar lavage fluid (BALF), reduced immunoglobulin E levels were measured in the sera, and increased interferon was detected in BALF from the recipients of CD38overexpressing BMDCs. Increased phosphorylatedp38 expression was also detected in LPSstimulated CD38overexpressing BMDCs, whereas pretreatment with a p38-specific inhibitor was able to abolish the effects of LPS stimulation and CD38 overexpression on IL-12 release and Th1 cell differentiation in BMDCs. These results suggested that CD38 may be involved in the DC function of alleviating asthma via restoration of the Th1/Th2 balance, thus providing a novel strategy for asthma therapy.