Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes
Tóm tắt
As a prototypical proinflammatory cytokine, interleukin-1 (IL-1) exacerbates the early post-stroke inflammation, whereas its neutralization is protective. To further investigate the underlying cell-type-specific IL-1 effects, we subjected IL-1 (α/β) knockout (Il1−/−) and wildtype (WT) littermate mice to permanent middle cerebral artery occlusion (pMCAO) and assessed immune cell infiltration and cytokine production in the ischemic hemisphere by flow cytometry 24 h and 72 h after stroke. Il1−/− mice showed smaller infarcts and reduced neutrophil infiltration into the ischemic brain. We identified γδ T cells and astrocytes as target cells of IL-1 signaling-mediated neutrophil recruitment. First, IL-1-induced IL-17A production in γδ T cells in vivo, and IL-17A enhanced the expression of the main neutrophil attracting chemokine CXCL1 by astrocytes in the presence of tumor necrosis factor (TNF) in vitro. Second, IL-1 itself was a potent activator of astrocytic CXCL1 production in vitro. By employing a novel FACS sorting strategy for the acute isolation of astrocytes from ischemic brains, we confirmed that IL-1 is pivotal for Cxcl1 upregulation in astrocytes in vivo. Our results underscore the pleiotropic effects of IL-1 on immune and non-immune cells within the CNS to mount and amplify the post-stroke inflammatory response.
Tài liệu tham khảo
Allen, C., Thornton, P., Denes, A., McColl, B. W., Pierozynski, A., Monestier, M., Pinteaux, E., Rothwell, N. J., & Allan, S. M. (2012). Neutrophil cerebrovascular transmigration triggers rapid neurotoxicity through release of proteases associated with decondensed DNA. The Journal of Immunology, 189(1), 381–392. https://doi.org/10.4049/jimmunol.1200409
Arumugam, T. V., Chan, S. L., Jo, D. G., Yilmaz, G., Tang, S. C., Cheng, A., Gleichmann, M., Okun, E., Dixit, V. D., Chigurupati, S., Mughal, M. R., Ouyang, X., Miele, L., Magnus, T., Poosala, S., Granger, D. N., & Mattson, M. P. (2006). Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nature Medicine, 12(6), 621–623. https://doi.org/10.1038/nm1403
Bach, A., Clausen, B. H., Møller, M., Vestergaard, B., Chi, C. N., Round, A., Sørensen, P. L., Nissen, K. B., Kastrup, J. S., Gajhede, M., Jemth, P., Kristensen, A. S., Lundström, P., Lambertsen, K. L., & Strømgaard, K. (2012). A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage. Proceedings of the National Academy of Sciences, 109(9), 3317–3322. https://doi.org/10.1073/pnas.1113761109
Batiuk, M. Y., De Vin, F., Duqué, S. I., Li, C., Saito, T., Saido, T., Fiers, M., Belgard, T. G., & Holt, M. G. (2017). An immunoaffinity-based method for isolating ultrapure adult astrocytes based on ATP1B2 targeting by the ACSA-2 antibody. Journal of Biological Chemistry, 292(21), 8874–8891. https://doi.org/10.1074/jbc.M116.765313
Boutin, H., LeFeuvre, R. A., Horai, R., Asano, M., Iwakura, Y., & Rothwell, N. J. (2001). Role of IL-1α and IL-1β in ischemic brain damage. Journal of Neuroscience, 21(15), 5528–5534. https://doi.org/10.1523/jneurosci.21-15-05528.2001
Chen, H., Eling, N., Martinez-Jimenez, C. P., O’Brien, L. M., Carbonaro, V., Marioni, J. C., Odom, D. T., & Roche, M. (2019). IL -7-dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti-tumour response. EMBO Reports. https://doi.org/10.15252/embr.201847379
Clarke, L. E., Liddelow, S. A., Chakraborty, C., Münch, A. E., Heiman, M., & Barres, B. A. (2018). Normal aging induces A1-like astrocyte reactivity. Proceedings of the National Academy of Sciences of the United States of America, 115(8), E1896–E1905. https://doi.org/10.1073/pnas.1800165115
Clausen, B. H., Lambertsen, K. L., Babcock, A. A., Holm, T. H., Dagnaes-hansen, F., & Finsen, B. (2008). Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice. Journal of Neuroinflammation. https://doi.org/10.1186/1742-2094-5-46
Clausen, B. H., Lambertsen, K. L., Dagnæs-Hansen, F., Babcock, A. A., von Linstow, C. U., Meldgaard, M., Kristensen, B. W., Deierborg, T., & Finsen, B. (2016). Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke. Acta Neuropathologica, 131(5), 775–791. https://doi.org/10.1007/s00401-016-1541-5
Dekens, D. W., Eisel, U. L. M., Gouweleeuw, L., Schoemaker, R. G., De Deyn, P. P., & Naudé, P. J. W. (2021). Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases. Ageing Research Reviews, 70, 101414. https://doi.org/10.1016/j.arr.2021.101414
Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J. P., Petzold, G. C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., Allen, N. J., Araque, A., Barbeito, L., Barzilai, A., Bergles, D. E., Bonvento, G., Butt, A. M., Chen, W. T., Cohen-Salmon, M., et al. (2021). Reactive astrocyte nomenclature, definitions, and future directions. Nature Neuroscience, 24(3), 312–325. https://doi.org/10.1038/s41593-020-00783-4
Foo, L. C., Allen, N. J., Bushong, E. A., Ventura, P. B., Chung, W. S., Zhou, L., Cahoy, J. D., Daneman, R., Zong, H., Ellisman, M. H., & Barres, B. A. (2011). Development of a method for the purification and culture of rodent astrocytes. Neuron, 71(5), 799–811. https://doi.org/10.1016/j.neuron.2011.07.022
Gelderblom, M., Gallizioli, M., Ludewig, P., Thom, V., Arunachalam, P., Rissiek, B., Bernreuther, C., Glatzel, M., Korn, T., Arumugam, T. V., Sedlacik, J., Gerloff, C., Tolosa, E., Planas, A. M., & Magnus, T. (2018). IL-23 (Interleukin-23)–producing conventional dendritic cells control the detrimental IL-17 (Interleukin-17) response in stroke. Stroke, 49(1), 155–164. https://doi.org/10.1161/strokeaha.117.019101
Gelderblom, M., Leypoldt, F., Steinbach, K., Behrens, D., Choe, C. U., Siler, D. A., Arumugam, T. V., Orthey, E., Gerloff, C., Tolosa, E., & Magnus, T. (2009). Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke, 40(5), 1849–1857. https://doi.org/10.1161/STROKEAHA.108.534503
Gelderblom, M., Weymar, A., Bernreuther, C., Velden, J., Arunachalam, P., Steinbach, K., Orthey, E., Arumugam, T. V., Leypoldt, F., Simova, O., Thom, V., Friese, M. A., Prinz, I., Hölscher, C., Glatzel, M., Korn, T., Gerloff, C., Tolosa, E., & Magnus, T. (2012). Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood, 120(18), 3793–3802. https://doi.org/10.1182/blood-2012-02-412726
Hasel, P., Rose, I. V. L., Sadick, J. S., Kim, R. D., & Liddelow, S. A. (2021). Neuroinflammatory astrocyte subtypes in the mouse brain. Nature Neuroscience, 24(10), 1475–1487. https://doi.org/10.1038/s41593-021-00905-6
Horai, R., Asano, M., Sudo, K., Kanuka, H., Suzuki, M., Nishihara, M., Takahashi, M., & Iwakura, Y. (1998). Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion. Journal of Experimental Medicine, 187(9), 1463–1475. https://doi.org/10.1084/jem.187.9.1463
Iadecola, C., Buckwalter, M. S., & Anrather, J. (2020). Immune responses to stroke: Mechanisms, modulation, and therapeutic potential. Journal of Clinical Investigation, 130(6), 2777–2788. https://doi.org/10.1172/JCI135530
Jin, M., Kim, J. H., Jang, E., Lee, Y. M., Soo Han, H., Woo, D. K., Park, D. H., Kook, H., & Suk, K. (2014). Lipocalin-2 deficiency attenuates neuroinflammation and brain injury after transient middle cerebral artery occlusion in mice. Journal of Cerebral Blood Flow and Metabolism, 34(8), 1306–1314. https://doi.org/10.1038/jcbfm.2014.83
Kapadia, R., Tureyen, K., Bowen, K. K., Kalluri, H., Johnson, P. F., & Vemuganti, R. (2006). Decreased brain damage and curtailed inflammation in transcription factor CCAAT/enhancer binding protein β knockout mice following transient focal cerebral ischemia. Journal of Neurochemistry, 98(6), 1718–1731. https://doi.org/10.1111/j.1471-4159.2006.04056.x
Lambertsen, K. L., Clausen, B. H., Babcock, A. A., Gregersen, R., Fenger, C., Nielsen, H. H., Haugaard, L. S., Wirenfeldt, M., Nielsen, M., Dagnaes-Hansen, F., Bluethmann, H., Færgeman, N. J., Meldgaard, M., Deierborg, T., & Finsen, B. (2009). Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. Journal of Neuroscience, 29(5), 1319–1330. https://doi.org/10.1523/JNEUROSCI.5505-08.2009
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W. S., Peterson, T. C., Wilton, D. K., Frouin, A., Napier, B. A., Panicker, N., Kumar, M., Buckwalter, M. S., Rowitch, D. H., Dawson, V. L., Dawson, T. M., et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 541(7638), 481–487. https://doi.org/10.1038/nature21029
Manwani, B., Liu, F., Scranton, V., Hammond, M. D., Sansing, L. H., & McCullough, L. D. (2013). Differential effects of aging and sex on stroke induced inflammation across the lifespan. Experimental Neurology, 249, 120–131. https://doi.org/10.1016/j.expneurol.2013.08.011
Mayo, L., Trauger, S. A., Blain, M., Nadeau, M., Patel, B., Alvarez, J. I., Mascanfroni, I. D., Yeste, A., Kivisäkk, P., Kallas, K., Ellezam, B., Bakshi, R., Prat, A., Antel, J. P., Weiner, H. L., & Quintana, F. J. (2014). Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nature Medicine, 20(10), 1147–1156. https://doi.org/10.1038/nm.3681
Maysami, S., Wong, R., Pradillo, J. M., Denes, A., Dhungana, H., Malm, T., Koistinaho, J., Orset, C., Rahman, M., Rubio, M., Schwaninger, M., Vivien, D., Bath, P. M., Rothwell, N. J., & Allan, S. M. (2016). A cross-laboratory preclinical study on the effectiveness of interleukin-1 receptor antagonist in stroke. Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X15606714
McCann, S. K., Cramond, F., Macleod, M. R., & Sena, E. S. (2016). Systematic review and meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke: An update. Translational Stroke Research, 7(5), 395–406. https://doi.org/10.1007/s12975-016-0489-z
Michael, B. D., Bricio-Moreno, L., Sorensen, E. W., Miyabe, Y., Lian, J., Solomon, T., Kurt-Jones, E. A., & Luster, A. D. (2020). Astrocyte- and neuron-derived CXCL1 drives neutrophil transmigration and blood-brain barrier permeability in viral encephalitis. Cell Reports, 32(11), 108150. https://doi.org/10.1016/j.celrep.2020.108150
Prince, L. R., Allen, L., Jones, E. C., Hellewell, P. G., Dower, S. K., Whyte, M. K. B., & Sabroe, I. (2004). The role of interleukin-1ß in direct and toll-like receptor 4-mediated neutrophil activation and survival. American Journal of Pathology, 165(5), 1819–1826. https://doi.org/10.1016/2Fs0002-9440(10)63437-2
Prinz, I., Sansoni, A., Kissenpfennig, A., Ardouin, L., Malissen, M., & Malissen, B. (2006). Visualization of the earliest steps of gammadelta T cell development in the adult thymus. Nature Immunology, 7(9), 995–1003. https://doi.org/10.1038/ni1371
Rajkovic, I., Wong, R., Lemarchand, E., Rivers-Auty, J., Rajkovic, O., Garlanda, C., Allan, S. M., & Pinteaux, E. (2018). Pentraxin 3 promotes long-term cerebral blood flow recovery, angiogenesis, and neuronal survival after stroke. Journal of Molecular Medicine, 96(12), 1319–1332. https://doi.org/10.1007/s00109-018-1698-6
Relton, J. K., & Rothwell, N. J. (1992). Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat. Brain Research Bulletin, 29(2), 243–246. https://doi.org/10.1016/0361-9230(92)90033-T
Rothhammer, V., Mascanfroni, I. D., Bunse, L., Takenaka, M. C., Kenison, J. E., Mayo, L., Chao, C. C., Patel, B., Yan, R., Blain, M., Alvarez, J. I., Kébir, H., Anandasabapathy, N., Izquierdo, G., Jung, S., Obholzer, N., Pochet, N., Clish, C. B., Prinz, M., et al. (2016). Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nature Medicine, 22(6), 586–597. https://doi.org/10.1038/nm.4106
Sadik, C. D., Kim, N. D., Alekseeva, E., & Luster, A. D. (2011). Il-17ra signaling amplifies antibody-induced arthritis. PLoS ONE, 6(10), e26342. https://doi.org/10.1371/journal.pone.0026342
Sims, J. E., & Smith, D. E. (2010). The IL-1 family: Regulators of immunity. Nature Reviews Immunology, 10(2), 89–102. https://doi.org/10.1038/nri2691
Stroemer, R. P., & Rothwell, N. J. (1998). Exacerbation of ischemic brain damage by localized striatal injection of interleukin-1β in the rat. Journal of Cerebral Blood Flow and Metabolism, 18(8), 833–839. https://doi.org/10.1097/00004647-199808000-00003
Sutton, C. E., Lalor, S. J., Sweeney, C. M., Brereton, C. F., Lavelle, E. C., & Mills, K. H. G. (2009). Interleukin-1 and IL-23 induce innate IL-17 production from γδ T cells, amplifying Th17 responses and autoimmunity. Immunity, 31(2), 331–341. https://doi.org/10.1016/j.immuni.2009.08.001
Tejima, E., Guo, S., Murata, Y., Arai, K., Lok, J., Leyen, K. V., Rosell, A., Wang, X., & Lo, E. H. (2009). Neuroprotective effects of overexpressing tissue inhibitor of metalloproteinase TIMP-1. Journal of Neurotrauma, 26, 1935–1941. https://doi.org/10.1089/2Fneu.2009.0959
Thornton, P., Pinteaux, E., Gibson, R. M., Allan, S. M., & Rothwell, N. J. (2006). Interleukin-1-induced neurotoxicity is mediated by glia and requires caspase activation and free radical release. Journal of Neurochemistry, 98(1), 258–266. https://doi.org/10.1111/j.1471-4159.2006.03872.x
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., & Speleman, F. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology, 3(7), research034. https://doi.org/10.1186/gb-2002-3-7-research0034
Williamson, M. R., Fuertes, C. J. A., Dunn, A. K., Drew, M. R., & Jones, T. A. (2021). Reactive astrocytes facilitate vascular repair and remodeling after stroke. Cell Reports, 35(4), 109048. https://doi.org/10.1016/j.celrep.2021.109048
Wong, R., Lénárt, N., Hill, L., Toms, L., Coutts, G., Martinecz, B., Császár, E., Nyiri, G., Papaemmanouil, A., Waisman, A., Müller, W., Schwaninger, M., Rothwell, N., Francis, S., Pinteaux, E., Denés, A., & Allan, S. M. (2019). Interleukin-1 mediates ischaemic brain injury via distinct actions on endothelial cells and cholinergic neurons. Brain, Behavior, and Immunity, 76, 126–138. https://doi.org/10.1016/j.bbi.2018.11.012
Yamasaki, Y., Matsuura, N., Shozuhara, H., Onodera, H., Itoyama, Y., & Kogure, K. (1995). Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke, 26(4), 676–680. https://doi.org/10.1161/01.str.26.4.676
Zamanian, J. L., Xu, L., Foo, L. C., Nouri, N., Zhou, L., Giffard, R. G., & Barres, B. A. (2012). Genomic analysis of reactive astrogliosis. Journal of Neuroscience, 32(18), 6391–6410. https://doi.org/10.1523/JNEUROSCI.6221-11.2012
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O’Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., Deng, S., Liddelow, S. A., Zhang, C., Daneman, R., Maniatis, T., Barres, B. A., & Wu, J. Q. (2014). An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. Journal of Neuroscience, 34(36), 11929–11947. https://doi.org/10.1523/JNEUROSCI.1860-14.2014