Role for Neuronally Derived Fractalkine in Mediating Interactions between Neurons and CX3CR1-Expressing Microglia
Open accessAbstract
A recently identified chemokine, fractalkine, is a member of the chemokine gene family, which consists principally of secreted, proinflammatory molecules. Fractalkine is distinguished structurally by the presence of a CX3C motif as well as transmembrane spanning and mucin-like domains and shows atypical constitutive expression in a number of nonhematopoietic tissues, including brain. We undertook an extensive characterization of this chemokine and its receptor CX3CR1 in the brain to gain insights into use of chemokine-dependent systems in the central nervous system. Expression of fractalkine in rat brain was found to be widespread and localized principally to neurons. Recombinant rat CX3CR1, as expressed in Chinese hamster ovary cells, specifically bound fractalkine and signaled in the presence of either membrane-anchored or soluble forms of fractalkine protein. Fractalkine stimulated chemotaxis and elevated intracellular calcium levels of microglia; these responses were blocked by anti-CX3CR1 antibodies. After facial motor nerve axotomy, dramatic changes in the levels of CX3CR1 and fractalkine in the facial nucleus were evident. These included increases in the number and perineuronal location of CX3CR1-expressing microglia, decreased levels of motor neuron-expressed fractalkine mRNA, and an alteration in the forms of fractalkine protein expressed. These data describe mechanisms of cellular communication between neurons and microglia, involving fractalkine and CX3CR1, which occur in both normal and pathological states of the central nervous system.
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The chemokine fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play an important role in neuroinflammation via paracrine signaling between neurons and microglia.
“The chemokine fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play an important role in neuroinflammation via paracrine signaling between neurons and microglia.[12][13][14]”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [14]
The Discussion (page not provided) identifies neurons as the primary source of fractalkine and microglia as the principal responding cells; it also links fractalkine–CX3CR1 signaling to the response to facial motor nerve injury. This supports neuron-to-microglia signaling in a pathological setting, but the paper does not establish a broad, important role in neuroinflammation specifically, and its evidence includes membrane-anchored as well as soluble fractalkine rather than solely paracrine signaling. (LLM, conf=0.82)
Experimental — accuracy not yet measuredCX3CR1 is selectively expressed in microglia and modulates microglial activity in response to fractalkine.
“The chemokine receptor CX3CR1 is selectively expressed in microglia and is thought to modulate their activity.”
From CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis (2010) · cites this paper as Harrison et al., 1998
Fractalkine through its receptor CX3CR1 acts as a repressor of microglia activation.
“Our findings support the concept that fractalkine through its receptor CX3CR1 (Harrison et al., 1998) acts as a repressor of microglia activation (Cardona et al., 2006).”
From CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis (2010) · cites this paper as Harrison et al., 1998
CX3CL1 is highly expressed within neurons.
“While CX3CR1 is expressed by many leukocyte cell types in the periphery, 15 in the brain CX3CR1 is exclusively expressed by microglia 13 whereas CX3CL1 is highly expressed within neurons.14”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [14]
Previous studies showed that in the CNS, CX3CL1 is expressed by neurons and signals to CX3CR1 on microglia.
“Previous studies showed that in the CNS, CX3CL1 is expressed by neurons and signals to CX3CR1 on microglia.13,14”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [14]
Immunosuppressor proteins including CX3CL1 and CD47 (to control microglial and macrophage function) and CFH (to control T-cell activation and block complement triggers) are already activated by neurodegeneration and block overproduction of pro-inflammatory signals.
“The immunosuppressor proteins, including CX3CL1 and CD47 (to control microglial and macrophage function) and CFH (to control T-cell activation and block complement triggers), are already activated by neurodegeneration and block the overproduction of pro-inflammatory signals (such as inducible nitric oxide synthase, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6) [61,62].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [62]
The CX3CR1 receptor expressed on microglia specifically recognizes CX3CL1 and is critical in neuron-microglia communication.
“Several studies have revealed that the CX3CR1 receptor expressed on microglia is critical in neuron-microglia communication. This receptor specifically recognizes the protein CX3CL1.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [251]
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Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396 · see citing works
Synthesis of Proteins by Native Chemical Ligation
Dawson, P. E., Muir, T. W., Clark‐Lewis, I., & Kent, S. B. H. (1994) · Science · doi:10.1126/science.7973629 · Cited by 4,142 · see citing works
Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.
Baggiolini, M., Dewald, B., & Moser, B. (1994) · PubMed · Cited by 2,232 · see citing works
Baggiolini, M., Dewald, B., & Moser, B. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.675 · Cited by 2,193 · see citing works
A new class of membrane-bound chemokine with a CX3C motif
Bazan, J. F., Bacon, K. B., Hardiman, G., Wang, W., Soo, K., Rossi, D., Greaves, D. R., Zlotnik, A., & Schall, T. J. (1997) · Nature · doi:10.1038/385640a0 · Cited by 2,013 · see citing works
Self-citationlnterleukin-8 and Related Chemotactic Cytokines—CXC and CC Chemokines
Baggiolini, M., Dewald, B., & Moser, B. (1993) · Advances in immunology · doi:10.1016/s0065-2776(08)60509-x · Cited by 1,672 · see citing works
Imai, T., Hieshima, K., Haskell, C. A., Baba, M., Nagira, M., Nishimura, M., Kakizaki, M., Takagi, S., Nomiyama, H., Schall, T. J., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80438-9 · Cited by 1,446 · see citing works
Functional plasticity of microglia: A review
Streit, W. J., Graeber, M. B., & Kreutzberg, G. W. (1988) · Glia · doi:10.1002/glia.440010502 · Cited by 937 · see citing works
Self-citationCCR3 and CCR5 are co-receptors for HIV-1 infection of microglia
He, J., Chen, Y., Farzan, M., Choe, H., Öhagen, Å., Gartner, S., Busciglio, J. A., Yang, X., Hofmann, W., Newman, W., et al. (1997) · Nature · doi:10.1038/385645a0 · Cited by 915 · see citing works
Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation
Pan, Y., Lloyd, C. M., Zhou, H., Dolich, S., Deeds, J., Gonzalo, J.-Á., Vath, J., Gosselin, M., Ma, J., Dussault, B. J., et al. (1997) · Nature · doi:10.1038/42491 · Cited by 643 · see citing works
Activation of dual T cell signaling pathways by the chemokine RANTES.
Bacon, K., Premack, B., Gardner, P., & Schall, T. (1995) · Science · doi:10.1126/science.7569902 · Cited by 518 · see citing works
Self-citationExpression of chemokine receptors by subsets of neurons in the central nervous system
Horuk, R., Martin, A. W., Wang, Z., Schweitzer, L., Gerassimides, A., Guo, H.-D., Lu, Z., Hesselgesser, J., Perez, H. D., Kim, J., et al. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.6.2882 · Cited by 385 · see citing works
Streit, W. J. (1990) · Journal of Histochemistry & Cytochemistry · doi:10.1177/38.11.2212623 · Cited by 372 · see citing works
Self-citationRottman, J. B., Ganley, K., Williams, K. C., Wu, L., Mackay, C. R., & Ringler, D. J. (1997) · Europe PMC (PubMed Central) · Cited by 273 · see citing works
Lavi, E., Strizki, J., Ulrich, A. M., Zhang, W., Fu, L., Wang, Q., O’Connor, M. J., Hoxie, J. A., & González‐Scarano, F. (1997) · Europe PMC (PubMed Central) · Cited by 238 · see citing works
Functional expression of the CXC-chemokine receptor-4/fusin on mouse microglial cells and astrocytes
Tanabe, S., Heesen, M. A., Yoshizawa, I., Berman, M. A., Luo, Y., Bleul, C. C., Springer, T. A., Okuda, K., Gerard, N. P., & Dorf, M. E. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.2.905 · Cited by 182 · see citing works
Chemokine receptor expression in cultured glia and rat experimental allergic encephalomyelitis
Jiang, Y. J., Salafranca, M. N., Adhikari, S., Xia, Y., Feng, L., Sonntag, M. K., deFiebre, C. M., Pennell, N. A., Streit, W. J., & Harrison, J. K. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00005-8 · Cited by 165 · see citing works
Self-citationFeng, L., Xia, Y., Yoshimura, T., et al. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117745 · Cited by 159 · see citing works
Self-citationThe role of microglia in brain injury.
Streit, W. R. (1997) · PubMed · Cited by 108 · see citing works
Self-citationRaport, C. J., Schweickart, V. L., Eddy, R. L., Shows, T. B., & Gray, P. W. (1995) · Gene · doi:10.1016/0378-1119(95)00336-5 · Cited by 95 · see citing works
Cloning, Chromosomal Localization, and RNA Expression of a Human β Chemokine Receptor-Like Gene
Combadière, C., Ahuja, S. K., & Murphy, P. M. (1995) · DNA and Cell Biology · doi:10.1089/dna.1995.14.673 · Cited by 88 · see citing works
McNamara, R. K., & Routtenberg, A. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(95)00083-5 · Cited by 85 · see citing works
Self-citationBacon, K. B., Camp, R. D. R., Cunningham, F. M., et al. (1988) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1988.tb11727.x · Cited by 76 · see citing works
Self-citationIdentification of Two Rat Genes Orthologous to the Human Interleukin-8 Receptors
Dunstan, C.-A. N., Salafranca, M. N., Adhikari, S., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32770 · Cited by 74 · see citing works
Self-citationHarrison, J. K., Barber, C. M., & Lynch, K. R. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90362-x · Cited by 54 · see citing works
Self-citationRat LCR1: cloning and cellular distribution of a putative chemokine receptor in brain.
Wong, M., Xin, W. W., & Duman, R. S. (1996) · PubMed · Cited by 46 · see citing works
Feng, L., Xia, Y., & Wilson, C. B. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42173-9 · Cited by 39 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 8
- [1]Baggiolini M, Dewald B, Moser B. Adv Immunol. 1994;55:97–179. [PubMed] [Google Scholar]
- [6]Rottman J B, Ganley K P, Williams K, Wu L, Mackay C R, Ringler D J. Am J Pathol. 1997;151:1341–1351. [PMC free article] [PubMed] [Google Scholar]
- [8]Wong M-L, Xin W W, Duman R S. Mol Psychiatry. 1996;1:133–140. [PubMed] [Google Scholar]
- [9]Tanabe S, Heesen M, Yoshizawa I, Berman M A, Luo Y, Bluel C C, Springer T A, Okuda K, Gerard N, Dorf M E. J Immunol. 1997;159:905–911. [PubMed] [Google Scholar]
- [10]Lavi E, Strizki J M, Ulrich A M, Zhang W, Fu L, Wang Q, O’Connor M, Hoxie J A, Gonzalez-Scarano F. Am J Pathol. 1997;151:1035–1042. [PMC free article] [PubMed] [Google Scholar]
- [11]Horuk R, Martin A W, Wang Z-X, Schweitzer L, Gerassimides A, Guo H, Lu Z-H, Hesselgesser J, Perez H D, Kim J, et al. J Immunol. 1997;158:2882–2890. [PubMed] [Google Scholar]
- [16]Feng L, Xia Y, Wilson C B. J Biol Chem. 1994;269:2342–2348. [PubMed] [Google Scholar]
- [27]Streit W J. Neurotoxicology. 1996;17:671–678. [PubMed] [Google Scholar]
Cited by
Sorted by citations
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175 · see citing works
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244 · see citing works
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · see citing works
Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
Self-citationControl of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · see citing works
Microglial Activation and Chronic Neurodegeneration
Lull, M. E., & Block, M. L. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.014 · Cited by 1,047 · see citing works
The Role of Microglia in the Healthy Brain: Figure 1.
Tremblay, M.-È., Stevens, B., Sierra, A., Wake, H., Bessis, A., & Nimmerjahn, A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4158-11.2011 · Cited by 992 · see citing works
Microglia as neuroprotective, immunocompetent cells of the CNS
Streit, W. J. (2002) · Glia · doi:10.1002/glia.10154 · Cited by 919 · see citing works
Self-citationMicroglia in Alzheimer's disease
Sarlus, H., & Heneka, M. T. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90606 · Cited by 911 · see citing works
The myeloid cells of the central nervous system parenchyma
Ransohoff, R. M., & Cardona, A. E. (2010) · Nature · doi:10.1038/nature09615 · Cited by 804 · see citing works
Regulation of Tau Pathology by the Microglial Fractalkine Receptor
Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.023 · Cited by 639 · see citing works
Kim, Y. S., & Joh, T. H. (2006) · Experimental & Molecular Medicine · doi:10.1038/emm.2006.40 · Cited by 655 · see citing works
Microglia: Dynamic Mediators of Synapse Development and Plasticity
Wu, Y., Dissing-Olesen, L., MacVicar, B. A., & Stevens, B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.008 · Cited by 661 · see citing works
CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity
Rogers, J. T., Morganti, J. M., Bachstetter, A. D., Hudson, C. E., Peters, M. M., Grimmig, B. A., Weeber, E. J., Bickford, P. C., & Gemma, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3667-11.2011 · Cited by 624 · see citing works
Holtman, I. R., Raj, D. D., Miller, J. A., Schaafsma, W., Yin, Z., Brouwer, N., Wes, P. D., Möller, T., Orre, M., Kamphuis, W., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0203-5 · Cited by 619 · see citing works
Austin, P. J., & Moalem-Taylor, G. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.08.013 · Cited by 607 · see citing works
The “quad‐partite” synapse: Microglia‐synapse interactions in the developing and mature CNS
Schafer, D. P., Lehrman, E. K., & Stevens, B. (2013) · Glia · doi:10.1002/glia.22389 · Cited by 570 · see citing works
Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease
Fuhrmann, M., Bittner, T., Jung, C. K. E., Burgold, S., Page, R. M., Mitteregger, G., Haass, C., LaFerla, F. M., Kretzschmar, H., & Herms, J. (2010) · Nature Neuroscience · doi:10.1038/nn.2511 · Cited by 562 · see citing works
The Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, K., Noctor, S. C., Lucassen, P. J., & Hol, E. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00566 · Cited by 516 · see citing works
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · see citing works
Cribbs, D. H., Berchtold, N. C., Perreau, V., Coleman, P. D., Rogers, J., Tenner, A. J., & Cotman, C. W. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-179 · Cited by 499 · see citing works
Do glia drive synaptic and cognitive impairment in disease?
Chung, W.-S., Welsh, C. A., Barres, B. A., & Stevens, B. (2015) · Nature Neuroscience · doi:10.1038/nn.4142 · Cited by 385 · see citing works
Immune and neuroendocrine mechanisms of stress vulnerability and resilience
Ménard, C., Pfau, M. L., Hodes, G. E., & Russo, S. J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.90 · Cited by 374 · see citing works
Hoshiko, M., Arnoux, I., Avignone, E., Yamamoto, N., & Audinat, E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1167-12.2012 · Cited by 384 · see citing works
“…local role of fractalkine in which cellular elements localized within the barrel hollows, possibly thalamic fibers, overexpress the chemokine at P5–P7 and thus favor directed migration of microglia (Harrison et al., 1998; Maciejewski-Lenoir et al., 1999) toward maturating thalamocortical synapses.”
BackgroundResultExpression of CX <sub>3</sub> CR1 chemokine receptors on neurons and their role in neuronal survival
Meucci, O., Fatatis, A., Simen, A. A., & Miller, R. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090017497 · Cited by 385 · see citing works
Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats
Bachstetter, A. D., Morganti, J. M., Jernberg, J., Schlunk, A., Mitchell, S. H., Brewster, K. W., Hudson, C. E., Cole, M. J., Harrison, J. K., Bickford, P. C., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.11.022 · Cited by 364 · see citing works
Self-citationFactors regulating microglia activation
Kierdorf, K., & Prinz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00044 · Cited by 360 · see citing works
Cai, Y., Liu, J., Wang, B., Sun, M., & Yang, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.856376 · Cited by 351 · see citing works
Mizutani, M., Pino, P. A., Saederup, N., Charo, I. F., Ransohoff, R. M., & Cardona, A. E. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1100421 · Cited by 346 · see citing works
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Chen, M., Luo, C., Zhao, J., Devarajan, G., & Xu, H. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.10.003 · Cited by 305 · see citing works
Microglia in Health and Disease
Ransohoff, R. M., & Khoury, J. E. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020560 · Cited by 303 · see citing works
Ishida, Y., Gao, J.-L., & Murphy, P. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.1.569 · Cited by 310 · see citing works
The identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308 · see citing works
The role of G protein-coupled receptors in the pathology of Alzheimer's disease
Thathiah, A., & De Strooper, B. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn2977 · Cited by 288 · see citing works
Glial activation and inflammation along the Alzheimer’s disease continuum
Nordengen, K., Kirsebom, B.-E., Henjum, K., Selnes, P., Gísladóttir, B., Wettergreen, M., Torsetnes, S. B., Grøntvedt, G. R., Waterloo, K. K., Aarsland, D., et al. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1399-2 · Cited by 274 · see citing works
Liu, Z., Condello, C., Schain, A., Harb, R., & Grutzendler, J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4403-10.2010 · Cited by 276 · see citing works
“Our findings support the concept that fractalkine through its receptor CX3CR1 (Harrison et al., 1998) acts as a repressor of microglia activation (Cardona et al., 2006).”
BackgroundXia, M. Q., Bacskai, B. J., Knowles, R. B., Qin, S. X., & Hyman, B. T. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00285-x · Cited by 269 · see citing works
Cho, S.-H., Sun, B., Zhou, Y., Kauppinen, T. M., Halabisky, B., Wes, P., Ransohoff, R. M., & Gan, L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.254268 · Cited by 268 · see citing works
Lipid and Lipoprotein Metabolism in Microglia
Loving, B. A., & Bruce, K. D. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00393 · Cited by 255 · see citing works
CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson’s disease
Pabon, M. M., Bachstetter, A. D., Hudson, C. E., Gemma, C., & Bickford, P. C. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-9 · Cited by 241 · see citing works
Hughes, P. M., Botham, M. S., Frentzel, S., Mir, A., & Perry, V. H. (2002) · Glia · doi:10.1002/glia.10037 · Cited by 252 · see citing works
Shao, F., Wang, X., Wu, H., Wu, Q., & Zhang, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.825086 · Cited by 250 · see citing works
The blood-brain barrier, chemokines and multiple sclerosis
Holman, D. W., Klein, R. S., & Ransohoff, R. M. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.07.019 · Cited by 247 · see citing works
Microglia Modulate Hippocampal Neural Precursor Activity in Response to Exercise and Aging
Vukovic, J., Colditz, M. J., Blackmore, D. G., Ruitenberg, M. J., & Bartlett, P. F. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5925-11.2012 · Cited by 241 · see citing works
How microglia sense and regulate neuronal activity
Umpierre, A. D., & Wu, L. (2021) · Glia · doi:10.1002/glia.23961 · Cited by 237 · see citing works
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Bolós, M., Llorens-Martín, M., Perea, J. R., Jurado-Arjona, J., Rábano, A., Hernández, F., & Avila, J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0200-1 · Cited by 231 · see citing works
Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge
Wynne, A. M., Henry, C. J., Huang, Y., Cleland, A., & Godbout, J. P. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.05.011 · Cited by 224 · see citing works
Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury
Soriano, S. G., Amaravadi, L. S., Wang, Y. F., Zhou, H., Yu, G. X., Tonra, J. R., Fairchild-Huntress, V., Fang, Q., Dunmore, J. H., Huszar, D., et al. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00033-4 · Cited by 222 · see citing works
Donnelly, D. J., Longbrake, E. E., Shawler, T. M., Kigerl, K. A., Lai, W., Tovar, C. A., Ransohoff, R. M., & Popovich, P. G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2114-11.2011 · Cited by 219 · see citing works
Modulating neurotoxicity through CX3CL1/CX3CR1 signaling
Limatola, C., & Ransohoff, R. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00229 · Cited by 210 · see citing works
Naert, G., & Rivest, S. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0299-11.2011 · Cited by 207 · see citing works
“CX3CL1 is primarily produced by neurons and signals via CX3CR1 within microglia and macrophages (Harrison et al., 1998; Cardona et al., 2006).”
BackgroundLyons, A., Lynch, A. M., Downer, E. J., Hanley, R., O’Sullivan, J. B., Smith, A., & Lynch, M. A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06253.x · Cited by 202 · see citing works
Microglial immune checkpoint mechanisms
Deczkowska, A., Amit, I., & Schwartz, M. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0145-x · Cited by 185 · see citing works
Wes, P. D., Holtman, I. R., Boddeke, E. W. G. M., Möller, T., & Eggen, B. J. L. (2016) · Glia · doi:10.1002/glia.22866 · Cited by 167 · see citing works
Effects of Microglia on Neurogenesis
Sato, K. (2015) · Glia · doi:10.1002/glia.22858 · Cited by 187 · see citing works
Reader, B. F., Jarrett, B. L., McKim, D. B., Wohleb, E. S., Godbout, J. P., & Sheridan, J. F. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.01.001 · Cited by 179 · see citing works
“Neuronal fractalkine expression, or lack thereof, is involved in microglial chemotaxis and calcium regulation and plays a fundamental role within neuronal and microglial communication (Harrison et al., 1998).”
BackgroundDysregulated neuronal–microglial cross-talk during aging, stress and inflammation
Jurgens, H. A., & Johnson, R. W. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2010.11.014 · Cited by 179 · see citing works
Periodontal microorganisms and Alzheimer disease – A causative relationship?
Jungbauer, G., Stähli, A., Zhu, X., Auber Alberi, L., Sculean, A., & Eick, S. (2022) · Periodontology 2000 · doi:10.1111/prd.12429 · Cited by 174 · see citing works
Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric Disorders
Stuart, M. J., Singhal, G., & Baune, B. T. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00357 · Cited by 163 · see citing works
Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation
Chu, E., Mychasiuk, R., Hibbs, M. L., & Semple, B. D. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02325-6 · Cited by 152 · see citing works
Molecular Mechanisms of Microglial Motility: Changes in Ageing and Alzheimer’s Disease
Franco-Bocanegra, D. K., McAuley, C., Nicoll, J. A. R., & Boche, D. (2019) · Cells · doi:10.3390/cells8060639 · Cited by 147 · see citing works
Mutant α-Synuclein Overexpression Mediates Early Proinflammatory Activity
Su, X., Federoff, H. J., & Maguire-Zeiss, K. A. (2009) · Neurotoxicity Research · doi:10.1007/s12640-009-9053-x · Cited by 145 · see citing works
Abutbul, S., Shapiro, J., Szaingurten‐Solodkin, I., Levy, N., Carmy, Y., Baron, R., Jung, S., & Monsonego, A. (2012) · Glia · doi:10.1002/glia.22343 · Cited by 122 · see citing works
The microglia in healthy and diseased retina
Li, L., Eter, N., & Heiduschka, P. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2015.04.020 · Cited by 112 · see citing works
Lauro, C., Di Angelantonio, S., Cipriani, R., Sobrero, F., Antonilli, L., Brusadin, V., Ragozzino, D., & Limatola, C. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.11.7590 · Cited by 110 · see citing works
Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy
Nash, K. R., Lee, D. C., Hunt, J. B., Morganti, J. M., Selenica, M.-L., Moran, P., Reid, P., Brownlow, M., Guang-Yu Yang, C., Savalia, M., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.011 · Cited by 108 · see citing works
Time-dependent effects of CX3CR1 in a mouse model of mild traumatic brain injury
Febinger, H. Y., Thomasy, H. E., Pavlova, M. N., Ringgold, K. M., Barf, P. R., George, A. M., Grillo, J. N., Bachstetter, A. D., Garcia, J. A., Cardona, A. E., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0386-5 · Cited by 110 · see citing works
“Data from some models of chronic neuronal injury suggest that CX3CR1 is protective because the absence of this receptor increases microglia activity and is associated with less favorable outcome [8, 12–16].”
Zujovic, V., Schussler, N., Jourdain, D., Duverger, D., & Taupin, V. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00259-4 · Cited by 102 · see citing works
Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation
Loving, B. A., Tang, M., Neal, M. C., Gorkhali, S., Murphy, R., Eckel, R. H., & Bruce, K. D. (2021) · Cells · doi:10.3390/cells10020198 · Cited by 105 · see citing works
Sandvig, I., Augestad, I. L., Håberg, A. K., & Sandvig, A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13959 · Cited by 94 · see citing works
Roseti, C., Fucile, S., Lauro, C., Martinello, K., Bertollini, C., Esposito, V., Mascia, A., Catalano, M., Aronica, E., Limatola, C., et al. (2013) · Epilepsia · doi:10.1111/epi.12354 · Cited by 92 · see citing works
Loss of tau rescues inflammation-mediated neurodegeneration
Maphis, N., Xu, G., Kokiko-Cochran, O. N., Cardona, A. E., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00196 · Cited by 91 · see citing works
White matter microglia heterogeneity in the CNS
Amor, S., McNamara, N. B., Gerrits, E., Marzin, M. C., Kooistra, S. M., Miron, V. E., & Nutma, E. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02389-x · Cited by 89 · see citing works
A Spirulina-Enhanced Diet Provides Neuroprotection in an α-Synuclein Model of Parkinson's Disease
Pabon, M. M., Jernberg, J. N., Morganti, J., Contreras, J., Hudson, C. E., Klein, R. L., & Bickford, P. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045256 · Cited by 90 · see citing works
Chen, X., Jiang, M., Li, H., Wang, Y., Shen, H., Li, X., Zhang, Y., Wu, J., Yu, Z., & Chen, G. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01882-6 · Cited by 85 · see citing works
Neuroinflammation in Huntington’s disease: From animal models to clinical therapeutics
Jia, Q., Li, S., Li, X.-J., & Yin, P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1088124 · Cited by 70 · see citing works
Suppression of LPS-induced tau hyperphosphorylation by serum amyloid A
Liu, J., Wang, D., Li, S.-Q., Yu, Y., & Ye, R. D. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0493-y · Cited by 58 · see citing works
Ischemia-induced Neuronal Cell Death Is Mediated by Chemokine Receptor CX3CR1
Wang, J., Gan, Y., Han, P., Yin, J., Liu, Q., Ghanian, S., Gao, F., Gong, G., & Tang, Z. (2018) · Scientific Reports · doi:10.1038/s41598-017-18774-0 · Cited by 58 · see citing works
“(5) Neutralizing the CX3CR1 with anti-CX3CR1 antibody could attenuate the damage of glutamate, (6) while the same animal source of anti-IgG antibody could not attenuate the damage.”
BackgroundYeo, S.-I., Kim, J.-E., Ryu, H. J., Seo, C. H., Lee, B. C., Choi, I.-G., Kim, D.-S., & Kang, T.-C. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.03.005 · Cited by 55 · see citing works
A New Generation of Drugs: Synthetic Peptides Based on Natural Regulatory Peptides
Kolomin, T., Shadrina, M., Slominsky, P., Limborska, S., & Myasoedov, N. (2013) · Neuroscience and Medicine · doi:10.4236/nm.2013.44035 · Cited by 30 · see citing works
Bemiller, S. M., Maphis, N. M., Formica, S. V., Wilson, G. N., Miller, C. M., Xu, G., Kokiko-Cochran, O. N., Kim, K.-W., Jung, S., Cannon, J. L., et al. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1310-6 · Cited by 24 · see citing works
Risk mitigation of immunogenicity: a key to personalized retinal gene therapy
Varin, J., Morival, C., Maillard, N., Adjali, O., & Cronin, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312818 · Cited by 19 · see citing works
- Authors
- Harrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., Botti, P., Bacon, K. B., & Feng, L.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Harrison, Jeffrey K.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-09
- Volume
- 95
- Issue
- 18
- Pages
- 10896-10901
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC27992
- OpenAlex
- W2163487275
- Cited by
- 1,176
- References
- 28
- Citations by year
- 2026: 29 · 2025: 37 · 2024: 41 · 2023: 49 · 2022: 51 · 2021: 65 · 2020: 54 · 2019: 45 · 2018: 53 · 2017: 33 · 2016: 48 · 2015: 56 · 2014: 71 · 2013: 52 · 2012: 44
- FWCI
- 17.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- University of Florida
- National Institutes of Health (7r29dk049832-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK49832)
- National Institute of Neurological Disorders and Stroke (NS 34901, R01NS034901)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fractalkine, CX3CR1, microglia, neurons, microglia-neuron interaction, chemokines, facial nerve axotomy, facial nucleus, motor neurons, microglial chemotaxis, intracellular calcium, central nervous system
- MeSH terms
- Amino Acid Sequence, Animals, Brain, Cloning, Molecular, Cricetinae, Male, Membrane Proteins, Molecular Sequence Data, Motor Neurons, Recombinant Fusion Proteins, CHO Cells, Rats, Sprague-Dawley, Microglia, Chemokines, CXC, Chemokines, CX3C, Rats, Chemokine CX3CL1
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