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The Viruses
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Chemokine receptors have been identified on cells and are important in that they aid entry of HIV in certain cell types. The first of these coreceptor proteins on host cells was initially called “fusin” and brought about fusion of CD4+ cells that were resistant to fusion and syncytial formation. Fusin (CXCR-4) is a member of a family of chemokine receptors. Recent studies indicate that macrophage-tropic viruses use CC chemokine 5 (CCR-5) as a principal coreceptor and to a lesser degree CCR-3. T cell-tropic viruses can employ CXCR-4. Persons with mutations changing the nature of these coreceptors may be protected from HIV infection or have a slower rate of progression to AIDS. Other receptors for HIV include galactosyl ceramide in glial cells and in some colon cell lines, Fc Receptors, and adhesion molecules on macrophages. These receptors may promote entry into key body sites such as the brain.
Integrins, Integrin Regulators, and the Extracellular Matrix
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
Stephen W. Hunt, Sirid-Aimée Kellermann, Yoji Shimizu
As discussed above, receptors for chemokines and other soluble factors are believed to be a particularly critical class of integrin regulators for leukocyte interactions with endothelium (2). The chemokines MCP-1, MIP-1α, MIP-1β, RANTES, and interferon (IFN)-inducible protein-10 (IP-10), as well as hepatocyte growth factor, have all been shown to induce up-regulation of β1 and/or β2 integrin-mediated adhesion of T cells to relevant counter-receptors and ECM ligands (49–52). Chemokine receptors belong to the seven-membrane-spanning family of G protein-coupled receptors (53). Chemokine-mediated inside-out signaling is believed to be particularly rapid in nature, inducing integrin activity within minutes of receptor engagement. Studies of mast cells suggest that mitogenic growth factors, such as stem cell factor and platelet-derived growth factor (PDGF), can also be classified as integrin regulators (54–57). Thus, other growth factor receptors that initiate the same downstream signaling pathways as the PDGF receptor may also function as integrin regulators.
Neuropathogenesis of viral infections
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Avindra Nath, Joseph R. Berger
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].
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).
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.
The RORγt-CCR6-CCL20 axis augments Th17 cells invasion into the synovia of rheumatoid arthritis patients
Published in Modern Rheumatology, 2018
Shunta Kaneko, Yuya Kondo, Masahiro Yokosawa, Kotona Furuyama, Seiji Segawa, Hiroto Tsuboi, Akihiro Kanamori, Isao Matsumoto, Masashi Yamazaki, Takayuki Sumida
Next, we addressed the issue of Th17 cell accumulation in inflamed joints. We showed that Th17 cells in RA patients highly expressed not only RORγt but also CCR6 in both peripheral blood and synovial fluid. Chemokine receptors, therefore, contribute to the migration of Th cells in response to their ligand [36–39]. Past studies reported that CCR6 was a Th17-specific chemokine receptor and induced migration in response to CCL20 [40–42]. Moreover, Hirota et al. revealed that the expression of CCR6 was regulated by RORγt [43]. These observations raised the possibility that the high expression of RORγt induced the upregulation of CCR6 in Th17 cells, resulting in the accumulation of Th17 cells in the inflamed joints of RA patients. To investigate this possibility, we performed migration (chemotaxis) assays using peripheral blood Th cells and showed that the migration index of rheumatoid Th17 cells to CCL20 was upregulated. Moreover, we showed that the concentration of CCL20 in synovial fluids was significantly higher than that of OA patients. These findings were consistent with some studies that the concentration of CCL20 in plasma and synovial fluids in RA patients was high [43,44], strongly suggesting that CCL20 was related with the accumulation of Th17 cells in RA patients.