Description

Introduction. Chemotactic receptors direct cells towards regions where there are high concentrations of chemokines.  In the presence of a gradient  of chemokines, these receptors organize a "molecular compass" that guides cells toward the highest concentration of these ligands. Chemoattraction allows migrating cells to find their correct position in the organism where they carry out their specialized functions, and therefore, this process 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. Although “chemotactic receptor” was the generic name given to these receptors, probably because chemotaxis was one of the first functions of them described by scientists, however, 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  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.