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CCR5

Chemokine receptors are receptors found on the surface of certain cells that interact with chemokines. They have a 7-transmembrane (7-TM) structure and couple to G-protein for signal transduction within a cell. [1] (Figure 1) Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux intracellular calcium (Ca2+) ions, initiate chemotaxis and guide the cell to a desired location. (Figure 2)

Figure 1. typical structure of a chemokine receptor.

Figure 2. the mechanism of interaction between a chemokine and a chemokine receptor.

Under the circumstances of inflammation, various kinds of cytokines, including chemokines, are released by the lesions. Guided by the chemokines, cells expressing chemokine receptors move towards the lesions where they can function better.[2] What’s more, different diseases would release different pools of chemokines, which would recruit different effector cells. See our disease table-chemokine

Based on the chemotaxis theory, in order to enhance the homing ability of our marvelous mesenchymal stem cells (MSCs) due to lack of enough chemokine receptors on their cell surface, we, SYSU-MEDICINE, had constructed a series of chemokine receptors that corresponding to different inflammatory diseases as far as possible. Among which, CCL5 is a significant chemokine (CCR5 is its chemokine receptor) in Myocardial Infarction and Experimental Allergic Encephalomyelitis(EAE) . See our disease table-chemokine

We acquired this gene from peripheral mononuclear blood cells (PMBCs) and purified it. (Figure 3) Then we constructed it under the control of EF-1α by Gateway technology. (Figure 4)

Figure 3 Purification of CCR5

Figure 4 EF-1α-CCR5.

Then, we tested the chemotaxis of engineered MSCs by conducting Transwell assay against CCL5. To our excitement, our engineered MSCs had improved their homing ability with chemokine receptor CCR5(Figure 5).

Figure 5. Transwell Assay of CCR5.

MIT MAHE 2020

Summary

CCR5 has been described as a major co-receptor of human immunodeficiency virus (HIV)-1 entry. CCR5 acts as a coreceptor for macrophage-tropic HIV isolates. The β-chemokines RANTES, macrophage inflammatory protein 1α (MIP-1α), and MIP-1β efficiently block infection by macrophage-tropic HIV strains at the CCR5 receptor site, presumably by competitive interaction.

References

[1]Allen, Samantha J.; Crown, Susan E.; Handel, Tracy M. (2007-01-01). "Chemokine: receptor structure, interactions, and antagonism". Annual Review of Immunology. 25: 787–820.

[2] Griffith J W, Sokol C L, Luster A D. Chemokines and chemokine receptors: positioning cells for host defense and immunity.[J]. Annual Review of Immunology, 2014, 32(1):659-702.

[3] Blanpain, C., Libert, F., Vassart, G., & Parmentier, M. (2002). CCR5 and HIV infection. Receptors & channels, 8(1), 19–31.

[4] Moore, J. P., Trkola, A., & Dragic, T. (1997). Co-receptors for HIV-1 entry. Current opinion in immunology, 9(4), 551–562. https://doi.org/10.1016/s0952-7915(97)80110-0

[5] Cao, Y., Qin, L., Zhang, L., Safrit, J., & Ho, D. D. (1995). Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. The New England journal of medicine, 332(4), 201–208. https://doi.org/10.1056/NEJM199501263320401

[6] Samson, M., Libert, F., Doranz, B. J., Rucker, J., Liesnard, C., Farber, C. M., Saragosti, S., Lapoumeroulie, C., Cognaux, J., Forceille, C., Muyldermans, G., Verhofstede, C., Burtonboy, G., Georges, M., Imai, T., Rana, S., Yi, Y., Smyth, R. J., Collman, R. G., Doms, R. W., … Parmentier, M. (1996). Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature, 382(6593), 722–725. https://doi.org/10.1038/382722a0

Sequence and Features