Effects Of Pulmonary Stromal Cells On Biological Characteristics Of Mature Dendritic Cells

Dendritic cells (DCs) are the most potent antigen-presenting cells (APC) in the immune system, which plays a central role in the immune response. DCs not only initiate immune respone through activating native T cells, but also suppress immune response by inducing immunotolerance. The double adjustment function of DCs helps maintain the immune balance. The final immune effect of DCs depends on its development stages and immune microenvironment which provides places for immune response and regulates immune response by controlling the differentiation, development and function of immune cells as well. Lungs interconnects with the outside enviornment through airway so it contacts with considerate external antigens everyday and yet manage to maintain the immune balance. Therefore, the lung must have precise mechanisms to maintain the immune balance. Our research confirms that the microenvironment of lungs has adjustment function on differentiation, development and function of DCs, which is closely related to the maintanance of immune response balance.ObjectivesTo observe effects of lung stromal cells on differentiation, development and function of mature dendritic cells (mDC) deriving from mouse bone marrow, thus further exploring its mechnisms.MethodsWe established the mouse lung stromal cells line and identified them by morphology and vimentin expression. The identification results showed that the primary cultured pulmonary stomal cells are fiborblast-like cells which highly secrete two inhibitory cytokines of TGF-βand VEGF detected by RT-PCR. The mDC were cultured in complete medium mixed with half of the supernatant of pulmonary stromal cells. One week later,the mDC was then induced into regulatory DCs (DCreg). The morphological characteristics, content of cytokines (IL-10 and IL-12p70) in the co-culture supernatants, expression of cellular phenotype and phagocytosis ability, inducing capacity of DCreg were detected by H-E staining, enzyme linked immunosorbent assay, fluorescence-activated cell sorting and MTT respectively. The difference between mDC and DCreg was then obsereved. Results:Compared with mDC, DCreg secreted more IL-10(P<0.01), and less IL-12p70 (P<0.01). As to the cellular phenotype, expression of CD11b were increased (P<0.01), while expression of CDllc,Ⅰa, CD86 decreased (P<0.01); phagocytosis ability of DCreg is lower than that of the mature dendritic cells (imDC) (P<0.01), and no significant difference was seen between DCreg and mDC (P> 0.05). and the capacity of inducing allograft T proliferation was lower than the mDC group.ConclusionsWe confirmed for the first time that pulmonary stromal cells can induce the mDC differentiating into DCreg, have the ablity of inhibiting allograft T cell proliferation,and negatively regulate immune response by inducing immunot-olerance. However,the exact mechanisms still remain unclear. Deep understa-nding of mechanisms of immune regulation on the lungs will greatly contribute to prevention and treatment of respiratory allergic diseases.