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Identification of molecular signatures for alternatively activated DC (AA-DC)

signalling dataset

Our lab has obtained data on the molecular signatures for alternatively activated DC.

This type of activation characterizes the state of DC in certain pathophysiological conditions, such as during the resolution of inflammation as well as in chronic inflammatory conditions and in tumors. AA-DC were obtained by culturing immature DC in the presence of a maturative agonists (such as, LPS, CD40L or TNF) and calcitriol, IL-10 or prostaglandin E2. AA-DC showed a decrease in the production of IL-12 but retained most of the ability to secrete other cytokines, such as TNF and CXCL8. The hallmark of AA-DC was the production of the angiogenic cytokine VEGF in vitro, and in vivo when the cells were implanted into the chicken embryo CAM assay. VEGF production by DC was selectively observed only when the DC where alternatively activated. Therefore, VEGF production by DC can be considered a signature of this state of activation. AA-DC induced in the presence of LPS and IL-10 also produced high levels of the long pentraxin PTX3. PTX3 is pattern recognition receptor that plays a pivotal role in humoral innate immunity. DC produced conspicuous amounts of PTX3 when stimulated with LPS and this production is further increased in the presence of IL-10. However, PTX3 production was not increased in other alternative conditions of activation, such as in the presence of dexamethasone or calcitriol. PTX3 has properties similar to antibodies. Its production is induced by pathogen recognition, it recognizes microbial moieties, activates complement and facilitates recognition by phagocytes. Thus, this long pentraxin behaves as a bona fide ante-antibody. In this perspective, it is interesting that IL-10 stimulates B cell differentiation and antibody production. Thus IL-10 stimulates the humoral arm of both innate (PTX3) and adaptive (antibodies) immunity.





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