Description
Introduction. Chemotactic receptors control a cell activity called chemoattraction, whereby they can direct a cell towards a region where there is a high concentration of a chemoattractant, e.g. a chemokine. Mechanistically, the fact that a receptor can regulate chemoattraction implies that in the presence of a gradient of a chemokine, this receptor has the ability to organize a "molecular compass" that guides this cell toward the highest concentration of this ligand. Therefore, the pair chemoattractant receptor/ligand, behave as "postal address" that allows migrating cells to find their correct position in the organism where they carry out their specialized functions. Hence chemoattraction, controlled by specific receptors and chemoattractantants, is crucial, both during development and in adult organisms. In the immune system, chemoattraction plays a key role in the control of innate and acquired immunity responses. Most interestingly, although “chemotactic receptor” was the generic name given to these receptors, probably because chemotaxis is certainly a quite impressive activity, they may also control additional cell functions, such as cytoarchitecture, survival, adhesion, migratory speed, endocytosis, and differentiation, among others. The characterization of the whole gamut of functions under the control of chemokine receptors, and the signaling mechanism involved to regulate them, can be important for a better understanding of the role played by these receptors in the immune system and to develop strategies to modulate the immune response. As this aspect of the biology of chemokine receptors has been largely neglected in the past years, this line of research may represent a novel field in the study of these receptors.
Project. Dendritic cells (DCs) are the most potent antigen-presenting cells known. These cells play a key role in the regulation of the immune response. To carry out this response properly, the CD should migrate to the lymph nodes, where they present antigens to T lymphocytes. This migration is directly by chemokine receptors CCR7 -ligands CCL19 and CCL21- and CXCR4 -ligand CXCL12-, which are both expressed by mature dendritic cells. Ligand CCL21 is expressed by lymphatic vessels and CCL19, CCL21, and CXCL12 in the lymph nodes proper.
Apart from chemotaxis, CCR7 regulates the survival, migration speed of the DCs. Other groups have reported that CCR7 also regulates endocytosis, the cytoarchitecture, and differentiation of DCs. We have found that CCR7 uses highly independent signaling modules with biased functionality to regulate these functions. In this project, we analyze the molecular mechanisms used by CCR7 to regulate all the functions described. Knowledge about the functions and signaling mechanisms used by CCR7, apart from contributing to a better understanding of the immune response, may be useful for the optimization of protocols that use CDs in antitumor therapies or the response to different threats including pathogens, like virus.
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