Polyunsaturated fatty acids and dendritic cells

Polyunsaturated fatty acids (PUFAs), particularly those of the n-3 series that are enriched in marine fish oils, are known to exert immunomodulatory effects. Beyond the influence of dietary fatty acid composition on the immune response, treatment with fish oil-derived PUFAs results in clinical benefits in various inflammatory diseases, such as rheumatoid arthritis. To initiate an immune response, molecules ("antigens") must be presented to antigen-specific "T" lymphocytes by so-called antigen-presenting cells. Dendritic cells are the most potent antigen-presenting cells. Dendritic cells in peripheral tissues are in an "immature" state and still have to be stimulated to maturate and become highly effective antigen-presenting cells. Hence interference with dendritic cell maturation, antigen presentation, or the interaction of dendritic cells with T lymphocytes could abolish initiation of an immune response. In contrast to numerous studies on lymphocytes, very little is known about PUFA effects on antigen-presenting cells in general and dendritic cells in particular. Therefore, this project aims at characterizing the influence of PUFAs on human dendritic cell maturation, antigen presentation, and interactions with T lymphocytes. Pilot experiments revealed PUFA-mediated alterations in dendritic cell surface molecules that are critically involved in antigen presentation and T cell interaction. In addition to a comprehensive characterization of PUFA effects on dendritic cell maturation and antigen presentation, this project will study possible molecular mechanisms underlying PUFA-mediated effects. These studies will primarily be focused on particular regions of the cell membrane, so-called "lipid rafts". Lipid rafts are enriched in saturated fatty acids under physiological conditions and are crucially involved in signal transduction. Thus, beyond investigating PUFA effects on crucial aspects of immune responses, this project will elucidate the role of lipid rafts in dendritic cell signal transduction and interaction with T lymphocytes. In conclusion, this project will considerably contribute to the understanding of PUFA-mediated immunomodulation and provide novel facts about the biology of dendritic cells that represent a central player in the immune system.

Polyunsaturated fatty acids (PUFAs), particularly those of the n-3 series that are enriched in marine fish oils, are known to exert immunomodulatory effects. Beyond the influence of dietary fatty acid composition on the immune response, treatment with fish oil-derived PUFAs results in clinical benefits in various inflammatory diseases, such as rheumatoid arthritis. To initiate an immune response, molecules ("antigens") must be presented to antigen-specific "T" lymphocytes by so-called antigen-presenting cells. Dendritic cells are the most potent antigen-presenting cells. Dendritic cells in peripheral tissues are in an "immature" state and still have to be stimulated to maturate and become highly effective antigen-presenting cells. Hence interference with dendritic cell maturation, antigen presentation, or the interaction of dendritic cells with T lymphocytes could abolish initiation of an immune response. In contrast to numerous studies on lymphocytes, very little is known about PUFA effects on antigen-presenting cells in general and dendritic cells in particular. Therefore, this project aims at characterizing the influence of PUFAs on human dendritic cell maturation, antigen presentation, and interactions with T lymphocytes. Pilot experiments revealed PUFA-mediated alterations in dendritic cell surface molecules that are critically involved in antigen presentation and T cell interaction. In addition to a comprehensive characterization of PUFA effects on dendritic cell maturation and antigen presentation, this project will study possible molecular mechanisms underlying PUFA-mediated effects. These studies will primarily be focused on particular regions of the cell membrane, so-called "lipid rafts". Lipid rafts are enriched in saturated fatty acids under physiological conditions and are crucially involved in signal transduction. Thus, beyond investigating PUFA effects on crucial aspects of immune responses, this project will elucidate the role of lipid rafts in dendritic cell signal transduction and interaction with T lymphocytes. In conclusion, this project will considerably contribute to the understanding of PUFA-mediated immunomodulation and provide novel facts about the biology of dendritic cells that represent a central player in the immune system.