Chemokine receptors in primary and secondary lymphoid tissues.

Chemokine receptors are a complex superfamily of surface G protein-coupled receptors present mostly in leukocytes. In this chapter, we review the presence and functions of chemokine receptors in the immune cells of the primary and secondary lymphoid organs. Those include bone marrow, thymus, spleen, lymph nodes, and Peyer's patches as the main components of the gut-associated lymphoid tissue. There are general groups of chemokine receptors: conventional and atypical. We will mostly cover the role of conventional chemokine receptors, which are divided into four classes (CC, CXC, CX3C, and XC). Some relevant members are CXCR4, CXCR5, CCR4 and CCR7. For example, CXCR4 is a key chemokine receptor in the bone marrow controlling from the homing of progenitor cells into the bone marrow, the development of B cells, to the homing of long-lived plasma cells to this primary lymphoid organ. CCR7 and CCR4 are two of the main players in the thymus. CCR7 along with CCR9 control the traffic of thymic seed progenitors into the thymus, while CCR4 and CCR7 are critical for the entry of thymocytes into the medulla and as controllers of the central tolerance in the thymus. CXCR4 and CXCR5 have major roles in the spleen, guiding the maturation and class-switching of B cells in the different areas of the germinal center. In the T-cell zone, CCR7 guides the differentiation of naïve T cells. CCR7 also controls and directs the entry of T cells, B cells, and dendritic cells into secondary lymphoid tissues, including the spleen and lymph nodes. As new technologies emerge, techniques such as high dimensional spectral flow cytometry or single-cell sequencing allow a more comprehensive knowledge of the chemokine receptor network and their ligands, as well as the discovery of new interactions mediating unknown and overlooked mechanisms in health and disease.