Cigarette smoke differentially modulates dendritic cell maturation and function in time

Background: Dendritic cells (DCs) as professional antigen presenting cells (APCs) play a critical role in the regulation of host immune responses. DCs evolve from immature, antigen-capturing cells, to mature antigen-presenting cells. The relative contribution of DCs to cigarette smoke-induced inflammation is not well documented. In the current study, we investigated a modulatory effect of cigarette smoke extract (CSE) on differentiation, maturation and function of DCs. Methods: Primary murine DCs were grown from bone marrow cells with GM-CSF. Development of DC was analyzed by expression of CD11c, MHCII, CD86, CD40 and CD83 using flow cytometry. Murine DC's and human L428 cells were co-cultured with CSE for various periods of time. Functional activity was analyzed by measuring FITC-dextran uptake, cytokine production and the ability to stimulate T cell activation in a mixed lymphocyte reaction. Results: Our results show that short-term CSE stimulation (similar to 24 h) influence the maturation status of newly differentiated and immature DCs towards more mature cells as revealed by upregulation of MHCII, CD83, CD86, CD40, reduction in antigen up-take capacity and enhanced secretion of pro-inflammatory (IL-12, IL-6 and TNF-alpha) cytokines. Interestingly, long-term CSE exposure, time-and concentration-dependently, suppressed the development of functional DCs. This suppression was demonstrated by a decline in CD11c/MHCII, CD83, CD86 and CD40 expression, the production of cytokines and ability to stimulate T lymphocytes. Moreover, CSE significantly suppressed the endocytosis function of mouse DCs which was not due to diminished DC viability. Similar to mouse DCs, long-term co-culturing of the human L428 DC cell line with CSE time-dependently suppressed the expression of CD54. Conclusions: The present study provides evidence that CSE modulates DC-mediated immune responses via affecting both the function and maturation of DCs. The suppressive effects of cigarette smoke on DC function might lead to impaired immune responses to various infections.