| Description: |
Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role []. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [], and endothelial cells, where they may act as either angiogenic or angiostatic factors [].The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors []. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [, ]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.This entry represents CXC chemokine receptor type 5 (CXCR5), also known as cluster of differentiation 185 or Burkitt lymphoma receptor 1, which acts as a receptor for CXCL13. Upon binding to CXCR5, it causes mobilisation of intracellular calcium and chemotaxis []. CXCR5 is specifically expressed in B cells and lymphatic tissues, as well as in spleen [, ]and is expressed by human CD34(-) mesenchymal progenitor cells and immortalized mesenchymal stem cell lines [].B lymphocytes expressing CXCR5 migrate in a concentration dependent manner in response to CXCL13, which does not induce chemotaxis in T lymphocytes, monocytes or neutrophils. This selectivity for B lymphocytes is unique among the chemokines. CXCR5 also plays an essential role in B cell migration [], lymphocyte homing []and in the development of normal lymphoid tissue [, ]. It has also been shown that CD4+CXCR5+ T cells expressing CXCR5 play a protective role in the immune response against mycobacterium tuberculosis (Mtb) infection, highlighting a potential use for TB vaccine design and therapy []. |
