Chemokines and Chemokine Receptor Interactions and Functions
Thomas R. O’Brien in Chemokine Receptors and AIDS, 2019
The expression of chemokine receptors is carefully regulated on lymphocytes with activation. The activating signals and the environment in which the lymphocyte is activated both determine the patterns of chemokines expressed (11). There are fundamental differences between naïve T cells, which are yet to encounter their cognate antigen, and memory/effector cells. Naïve T cells express high levels of both L-selectin, an adhesion molecule that promotes binding to endothelium in lymph nodes, and CCR7. The ligands for CCR7 are two chemokines that are constitutively expressed in lymphoid tissue, SLC, which is found on high endothelial venules and ELC, which is made by interdigitating dendritic cells in the T cell areas of the lymph node (32). Thus, naïve T cells will be recruited to the T cell areas of lymphoid tissue where they can be efficiently activated by antigen presented by dendritic cells.
Neuropathogenesis of viral infections
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Since the brain has few immune effector cells, induction of chemoattractant cytokines called chemokines may be an important defense mechanism, where by the brain under attack from viruses, may recruit lymphocytic and monocytic cells to the brain. However, if the virus is capable of infecting the lymphocytes or monocytes, these cells may carry the pathogen with them. Also, if the uninfected cells get activated and are present in large numbers, they may produce cytotoxic substances that may damage host cells in the brain. All cell types within the brain are capable chemokines. To date, there are nearly 50 different chemokine receptors and an equal number of chemokines identified. Multiple terms have been used by different research groups to name the same chemokine, making the field difficult to follow. Further, one chemokine receptor may respond to several different chemokines and one chemokine may interact with more than one type of chemokine receptor [48]. Nonetheless, some common themes have emerged. For example, MCP-1/CCL-2 is the major chemokine for monocyte infiltration to the brain. Levels of MCP-1/CCL-2 are elevated in CSF of patients with HIV dementia [49] and CMV encephalitis [50].
C-C Chemokine Receptors
Richard Horuk in Chemoattractant Ligands and Their Receptors, 2020
In sharp contrast to CXC chemokine receptors where only two receptor subtypes account for binding of all the different CXC chemokines, there are at least 4 different C-C chemokines receptors that have been identified by molecular cloning. Pharmacological characterization of chemokine receptors has implied that there are not more then 4 receptor subtypes on different subpopulations of leukocytes. However, preliminary characterization of the cloned C-C chemokine receptors suggests that different receptor subtypes have the capacity to interact with identical ligands. This implies that effector cells will only respond to a given chemokine if a particular receptor is expressed in that cell. This feature might explain why some C-C chemokines have a preference for a specific subset of leukocytes. Alternatively, the temporal and spatial expression of chemokine expression could dictate the homing and preferential migration of leukocytes to areas of immune reactivity. With the availability of cloned receptors, structure/function analysis should define motifs important for chemokine binding and coupling to signal transduction pathways. Furthermore, a better understanding of the expression and biochemical and pharmacological characteristics of a given C-C chemokine receptor will soon be unraveled. These types of avenues will be crucial in understanding how ligand binding leads to receptor activation and eventually cell motility and activation.
Cancer and immunity: who is shaping whom?
Published in International Reviews of Immunology, 2021
Chemokines are small-size cytokine-like proteins secreted by different immune and nonimmune cells that mainly facilitate immune cell movement toward higher concentration through chemokine receptors. Various classes of chemokine are produced by cells, and they play an important role in various immunological processes such as inflammation and immune homeostasis. The expression and function of chemokines alter significantly in various infectious and noninfectious diseases. The third review article in this issue by Zangouei et al. discusses the role of chemokines in bladder cancer. The article describes the interaction between immune cells and bladder cancer tissues and discusses the role of an immune activator (Bacille Calmette-Guerin vaccine) in the treatment of bladder cancer. It also highlights the importance of chemokines and chemokine receptors as a marker for the early detection of this cancer, as well as for cancer progression and metastasis [3]. This article will be of particular interest to oncoimmunologists and immunologists working on the fundamental and/or developmental aspects of cancer diagnostics (Figure 1).
Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate
Published in Annals of Medicine, 2021
Hussam A. S. Murad, Misbahuddin M. Rafeeq, Thamer M. A. Alqurashi
There are two types of chemokine receptors (CKRs): conventional (cCKRs) and atypical (ACKRs). Currently, there are 18 cCKRs and four ACKRs annotated according to the predominant type of chemokine they bind. cCKRs are G-protein coupled receptors with downstream intracellular signalling, mainly including heterotrimeric G-proteins, β-arrestins and JAK‐STAT pathways. ACKRs are primarily regarded as scavenger receptors and appear to function independently of G-protein signalling pathways; nonetheless, they appear to play a role in regulating chemokine localization and function, thereby indirectly controlling interactions between chemokines and cCKRs. However, there is some controversy regarding the exact molecular mechanisms underlying the functions of ACKRs and their crosstalk with cCKRs [10]. Receptor specificity is complex, with many chemokines binding to several different CKRs; a particular CKR may have many different chemokine ligands and some non-chemokine ligands.
CCR5 is a potential therapeutic target for cancer
Published in Expert Opinion on Therapeutic Targets, 2021
Hossein Hemmatazad, Martin D. Berger
Chemokine receptors mediate the interaction between chemokines and different immune cell types and comprise a large family of seven transmembrane domain G-protein-coupled receptors [16]. These chemokine receptors are classified according to the subgroup of chemokines they bind (CXCR, CCR, XCR, CX3CR) [17]. Every single receptor can be either activated by one or many different chemokines with various affinity, efficacy and downstream cellular responses [18]. In 1996, Samson et al. cloned the ChemR13 human gene, characterizing a new CC chemokine receptor [19]. This new CC chemokine receptor was designated as CC-CKR5, as it was the fifth functionally identified receptor in its class and responded physiologically to macrophage inflammatory protein-1α (MIP-1α or CCL3), MIP-1β (or CCL4) and regulated on activation normal T cell expressed and secreted protein (RANTES or CCL5) [19]. Figure 1 illustrates the plethora of chemokines with binding affinity to CCR5 exerting both agonistic (right) and antagonistic effects (left).
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