Th17 lymphocytes induce neuronal cell death in a human iPSC-based model of Parkinson's disease
Open accessAbstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death inducers of induced pluripotent stem cell (iPSC)-derived MBNs in sporadic PD. Higher Th17 frequencies were found in the blood of PD patients and increased numbers of T lymphocytes were detected in postmortem PD brain tissues. We modeled this finding using autologous co-cultures of activated T lymphocytes and iPSC-derived MBNs of sporadic PD patients and controls. After co-culture with T lymphocytes or the addition of IL-17, PD iPSC-derived MBNs underwent increased neuronal death driven by upregulation of IL-17 receptor (IL-17R) and NFκB activation. Blockage of IL-17 or IL-17R, or the addition of the FDA-approved anti-IL-17 antibody, secukinumab, rescued the neuronal death. Our findings indicate a critical role for IL-17-producing T lymphocytes in sporadic PD.
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Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221 · see citing works
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
Systematic review of levodopa dose equivalency reporting in Parkinson's disease
Tomlinson, C. L., Stowe, R. L., Patel, S., Rick, C., Gray, R. G., & Clarke, C. E. (2010) · Movement Disorders · doi:10.1002/mds.23429 · Cited by 4,232 · see citing works
Immunopathology of multiple sclerosis
Dendrou, C. A., Fugger, L., & Friese, M. A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3871 · Cited by 2,215 · see citing works
How neuroinflammation contributes to neurodegeneration
Ransohoff, R. M. (2016) · Science · doi:10.1126/science.aag2590 · Cited by 1,967 · cited 11× · see citing works
“CNS-infiltrating Th17 cells were shown to induce neurodegeneration in the MPTP mouse model by direct interaction with neurons via the adhesion molecules LFA-1 and ICAM-1 expressed on Th17 cells and neurons, respectively (Kawanokuchi et al., 2008; Liu et al., 2016).”
BackgroundInfluentialSoldner, F., Hockemeyer, D. F., Beard, C., Gao, Q., Bell, G. W., Cook, E. G., Hargus, G., Blak, A. A., Cooper, O., Mitalipova, M. M., et al. (2009) · Cell · doi:10.1016/j.cell.2009.02.013 · Cited by 1,546 · see citing works
Brochard, V., Combadière, B., Prigent, A., Laouar, Y., Perrin, A., Beray-Berthat, V., Bonduelle, O., Alvarez-Fischer, D., Callebert, J., Launay, J.-M., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36470 · Cited by 1,172 · see citing works
T cells from patients with Parkinson’s disease recognize α-synuclein peptides
Sulzer, D., Alcalay, R. N., Garretti, F., Cote, L., Kanter, E., Agin-Liebes, J., Liong, C., McMurtrey, C., Hildebrand, W. H., Mao, X., et al. (2017) · Nature · doi:10.1038/nature22815 · Cited by 866 · see citing works
LRRK2 Mutant iPSC-Derived DA Neurons Demonstrate Increased Susceptibility to Oxidative Stress
Nguyen, H. N., Byers, B., Cord, B. J., Shcheglovitov, A., Byrne, J., Gujar, P., Kee, K., Schüle, B., Dolmetsch, R. E., Langston, J. W., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.01.013 · Cited by 748 · see citing works
Blood–brain barrier dysfunction in parkinsonian midbrain in vivo
Kortekaas, R., Leenders, K. L., van Oostrom, J. C. H., Vaalburg, W., Bart, J., Willemsen, A. T. M., & Hendrikse, N. H. (2005) · Annals of Neurology · doi:10.1002/ana.20369 · Cited by 733 · see citing works
Efficient derivation of microglia-like cells from human pluripotent stem cells
Muffat, J., Li, Y., Yuan, B., Mitalipova, M., Omer, A., Corcoran, S., Bakiasi, G., Tsai, L.-H., Aubourg, P., Ransohoff, R. M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4189 · Cited by 651 · see citing works
Pluripotent stem cells in disease modelling and drug discovery
Avior, Y., Sagi, I., & Benvenisty, N. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.27 · Cited by 592 · see citing works
Neuroinflammation in Parkinson's disease
Hirsch, E. C., Vyas, S., & Hunot, S. (2012) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(11)70065-7 · Cited by 586 · see citing works
Sánchez‐Danés, A., Richaud‐Patín, Y., Carballo‐Carbajal, I., Jiménez‐Delgado, S., Caig, C., Mora, S., Guglielmo, C. D., Ezquerra, M., Patel, B., Giralt, A., et al. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201200215 · Cited by 557 · see citing works
Reinhardt, P., Glatza, M., Hemmer, K., Tsytsyura, Y., Thiel, C. S., Höing, S., Moritz, S., Parga, J. A., Wagner, L., Bruder, J. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059252 · Cited by 443 · see citing works
Ryan, S. D., Dolatabadi, N., Chan, S. F., Zhang, X., Akhtar, M. W., Parker, J., Soldner, F., Sunico, C. R., Nagar, S., Talantova, M. V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.009 · Cited by 430 · see citing works
Reynolds, A. D., Stone, D. K., Hutter, J. A. L., Benner, E., Mosley, R., & Gendelman, H. E. (2010) · Journal of Immunology · doi:10.4049/jimmunol.0901852 · Cited by 391 · see citing works
Imaizumi, Y., Okada, Y., Akamatsu, W., Koike, M., Kuzumaki, N., Hayakawa, H., Nihira, T., Kobayashi, T., Ohyama, M., Sato, S., et al. (2012) · Molecular Brain · doi:10.1186/1756-6606-5-35 · Cited by 378 · see citing works
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349 · see citing works
MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration
Cebrián, C., Zucca, F. A., Mauri, P., Steinbeck, J. A., Studer, L., Scherzer, C. R., Kanter, E., Budhu, S., Mandelbaum, J., Vonsattel, J. P., et al. (2014) · Nature Communications · doi:10.1038/ncomms4633 · Cited by 338 · see citing works
Alterations of T-lymphocyte populations in Parkinson disease
Baba, Y., Kuroiwa, A., Uitti, R. J., Wszolek, Z. K., & Yamada, T. (2005) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2005.07.005 · Cited by 336 · see citing works
Byers, B., Cord, B. J., Nguyen, H. N., Schüle, B., Fenno, L. E., Lee, P. C., Deisseroth, K. A., Langston, J. W., Pera, R. A. R., & Palmer, T. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026159 · Cited by 295 · see citing works
Lymphocyte populations in Parkinson's disease and in rat models of parkinsonism
Bas, J. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00422-7 · Cited by 250 · see citing works
Production and functions of IL-17 in microglia
Kawanokuchi, J., Shimizu, K., Nitta, A., Yamada, K., Mizuno, T., Takeuchi, H., & Suzumura, A. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2007.11.006 · Cited by 249 · see citing works
Inflammation and Adaptive Immunity in Parkinson's DiseasePreprint
Mosley, R. L., Hutter-Saunders, J. A. L., Stone, D. K., & Gendelman, H. E. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009381 · Cited by 246 · see citing works
Vulnerability of Human Neurons to T Cell-Mediated Cytotoxicity1
Giuliani, F., Goodyer, C., Antel, J., & Yong, W. V. (2003) · Journal of Immunology · doi:10.4049/jimmunol.171.1.368 · Cited by 238 · see citing works
Reduced T helper and B lymphocytes in Parkinson's disease
Stevens, C. H., Rowe, D. B., Morel‐Kopp, M., Orr, C., Russell, T., Ranola, M., Wård, C., & Halliday, G. M. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.07.015 · Cited by 189 · see citing works
Kapeli, K., Pratt, G. A., Vu, A. Q., Hutt, K. R., Martinez, F. J., Sundararaman, B., Batra, R., Freese, P., Lambert, N. J., Huelga, S. C., et al. (2016) · Nature Communications · doi:10.1038/ncomms12143 · Cited by 169 · see citing works
Self-citationShaltouki, A., Sivapatham, R., Pei, Y., Gerencser, A. A., Momčilović, O., Rao, M. S., & Zeng, X. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.02.019 · Cited by 127 · see citing works
Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons
Havlicek, S., Kohl, Z., Mishra, H. K., Prots, I., Eberhardt, E., Denguir, N., Wend, H., Plötz, S., Boyer, L. F., Marchetto, M. C., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt644 · Cited by 122 · see citing works
Self-citationLiu, Z., Huang, Y., Cao, B.-B., Qiu, Y.-H., & Peng, Y.-P. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-0249-9 · Cited by 112 · see citing works
The Trojan horse - neuroinflammatory impact of T cells in neurodegenerative diseases
Sommer, A., Winner, B., & Prots, I. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0222-8 · Cited by 80 · see citing works
Self-citationThe expression of PARP, NF-κB and parvalbumin is increased in Parkinson disease
Soós, J., Engelhardt, J. I., Siklós, L., Havas, L., & Majtényi, K. (2004) · Neuroreport · doi:10.1097/01.wnr.0000136175.51954.ce · Cited by 73 · see citing works
Ohta, E., Nihira, T., Uchino, A., Imaizumi, Y., Okada, Y., Akamatsu, W., Takahashi, K., Hayakawa, H., Nagai, M., Ohyama, M., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv212 · Cited by 70 · see citing works
Borgs, L., Peyre, E., Alix, P., Hanon, K., Grobarczyk, B., Godin, J., Purnelle, A., Krusy, N., Maquet, P., Lefebvre, P., et al. (2016) · Scientific Reports · doi:10.1038/srep33377 · Cited by 65 · see citing works
Infiltrating T lymphocytes reduce myeloid phagocytosis activity in synucleinopathy model
Sommer, A., Fadler, T., Dorfmeister, E., Hoffmann, A.-C., Xiang, W., Winner, B., & Prots, I. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0632-5 · Cited by 62 · see citing works
Self-citationCutforth, T., DeMille, M. M. C., Agalliu, I., & Agalliu, D. (2016) · Future Neurology · doi:10.2217/fnl.16.4 · Cited by 56 · see citing works
Induced pluripotent stem cell technology for the study of human disease
Lee, G., & Studer, L. (2009) · Nature Methods · doi:10.1038/nmeth.f.283 · Cited by 52 · see citing works
Flagged first, then by citations
1 of the 39 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
IL-17 and IL-17-producing cells in protection versus pathology
Mills, K. H. G. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00746-9 · Cited by 1,023 · see citing works
Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health
Parker, A., Fonseca, S., & Carding, S. R. (2019) · Gut Microbes · doi:10.1080/19490976.2019.1638722 · Cited by 722 · see citing works
Intestinal infection triggers Parkinson's disease-like symptoms in Pink1(-/-) mice
Matheoud, D., Cannon, T., Voisin, A., Penttinen, A.-M., Ramet, L., Fahmy, A. M., Ducrot, C., Laplante, A., Bourque, M.-J., Zhu, L., et al. (2019) · Nature · doi:10.1038/s41586-019-1405-y · Cited by 496 · see citing works
PINK1/PARKIN signalling in neurodegeneration and neuroinflammation
Quinn, P. M. J., Moreira, P. I., Ambrósio, A. F., & Alves, C. H. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01062-w · Cited by 486 · see citing works
Parkinson disease and the immune system - Associations, mechanisms and therapeutics
Tan, E.-K., Chao, Y.-X., West, A., Chan, L.-L., Poewe, W., & Jankovic, J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0344-4 · Cited by 457 · see citing works
Signaling pathways in Parkinson’s disease: molecular mechanisms and therapeutic interventions
Xu, D.-C., Chen, Y., Xu, Y., Chen-Yu, S., & Peng, L.-H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01353-3 · Cited by 442 · see citing works
Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications
Cerneckis, J., Cai, H., & Shi, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01809-0 · Cited by 452 · see citing works
CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson's disease
Williams, G. P., Schonhoff, A. M., Jurkuvenaite, A., Corbin-Stein, N. J., Standaert, D. G., & Harms, A. S. (2021) · Brain · doi:10.1093/brain/awab103 · Cited by 308 · see citing works
The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options
Wang, Q., Luo, Y., Ray Chaudhuri, K., Reynolds, R., Tan, E.-K., & Pettersson, S. (2021) · Brain · doi:10.1093/brain/awab156 · Cited by 281 · see citing works
Najjar, S., Najjar, A., Chong, D. J., Pramanik, B. K., Kirsch, C., Kuzniecky, R., Pacia, S. V., & Azhar, S. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01896-0 · Cited by 282 · see citing works
The Contribution of Microglia to Neuroinflammation in Parkinson’s Disease
Badanjak, K., Fixemer, S., Smajić, S., Skupin, A., & Grünewald, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094676 · Cited by 281 · see citing works
Periphery and brain, innate and adaptive immunity in Parkinson’s disease
Harms, A. S., Ferreira, S. A., & Romero‐Ramos, M. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02268-5 · Cited by 279 · see citing works
STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy
Hinkle, J. T., Patel, J., Panicker, N., Karuppagounder, S. S., Biswas, D., Belingon, B., Chen, R., Brahmachari, S., Pletnikova, O., Troncoso, J. C., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2118819119 · Cited by 240 · see citing works
IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease
Brigas, H. C., Ribeiro, M. A., Coelho, J. E., Gomes, R., Gómez‐Murcia, V., Carvalho, K., Faivre, É., Costa-Pereira, S., Darrigues, J., de Almeida, A. A., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109574 · Cited by 232 · see citing works
CD4 + T cells contribute to neurodegeneration in Lewy body dementia
Gate, D., Tapp, E., Leventhal, O., Shahid, M., Nonninger, T. J., Yang, A. C., Strempfl, K., Unger, M. S., Fehlmann, T., Oh, H. S., et al. (2021) · Science · doi:10.1126/science.abf7266 · Cited by 209 · see citing works
Liu, Z., Qiu, A.-W., Huang, Y., Yang, Y., Chen, J.-N., Gu, T.-T., Cao, B.-B., Qiu, Y.-H., & Peng, Y.-P. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.07.026 · Cited by 207 · see citing works
Ten Unsolved Questions About Neuroinflammation in Parkinson's Disease
Hirsch, É. C., & Standaert, D. G. (2020) · Movement Disorders · doi:10.1002/mds.28075 · Cited by 191 · see citing works
Neuroinflammation and Parkinson’s Disease—From Neurodegeneration to Therapeutic Opportunities
Araújo, B., Caridade-Silva, R., Soares-Guedes, C., Martins‐Macedo, J., Gomes, E. D., Monteiro, S., & Teixeira, F. G. (2022) · Cells · doi:10.3390/cells11182908 · Cited by 198 · see citing works
Neuroinflammation and protein pathology in Parkinson’s disease dementia
Kouli, A., Camacho, M., Allinson, K. S. J., & Williams‐Gray, C. H. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01083-5 · Cited by 187 · see citing works
Genetic predispositions of Parkinson’s disease revealed in patient-derived brain cells
Tran, J., Anastacio, H. T. D., & Bardy, C. (2020) · npj Parkinson s Disease · doi:10.1038/s41531-020-0110-8 · Cited by 181 · see citing works
Copas, A. N. M., McComish, S. F., Fletcher, J. M., & Caldwell, M. A. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.666737 · Cited by 175 · see citing works
Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?
Mayne, K., White, J. A., McMurran, C. E., Rivera, F. J., & de la Fuente, A. G. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.572090 · Cited by 167 · see citing works
Ni, P., Dong, H., Wang, Y., Zhou, Q., Xu, M., Qian, Y., & Sun, J. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1374-3 · Cited by 160 · see citing works
Autoimmunity in Parkinson's Disease: The Role of α-Synuclein-Specific T Cells
Garretti, F., Agalliu, D., Arlehamn, C. S. L., Sette, A., & Sulzer, D. L. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00303 · Cited by 162 · see citing works
Liu, L., Li, Y., Peng, H., Liu, R., Ji, W., Shi, Z., Shen, J., Ma, G., & Zhang, X. (2020) · Science Advances · doi:10.1126/sciadv.aba3967 · Cited by 162 · see citing works
Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases
Chen, J., Liu, X., & Zhong, Y. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.566922 · Cited by 154 · see citing works
Immunosenescence: signaling pathways, diseases and therapeutic targets
Fu, Y., Wang, B., Alu, A., Hong, W., Hong, L., He, X., Shi, H., Cheng, P., & Yang, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02371-z · Cited by 157 · see citing works
Probiotics may have beneficial effects in parkinson’s disease: In vitro evidence
Magistrelli, L., Amoruso, A., Mogna, L., Graziano, T., Cantello, R., Pane, M., & Comi, C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00969 · Cited by 144 · see citing works
The immune system in Parkinson's disease: what we know so far
Roodveldt, C., Bernardino, L. I., Çakmak, Ö. Ö., Dragić, M., Fladmark, K. E., Ertan, S., Aktaş, B., Pita, C., Ciglar, L., Garraux, G., et al. (2024) · Brain · doi:10.1093/brain/awae177 · Cited by 148 · see citing works
The Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases
Zang, X., Chen, S., Zhu, J., Ma, J., & Zhai, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.872134 · Cited by 139 · see citing works
Panagiotakopoulou, V., Ivanyuk, D., Cicco, S. D., Haq, W., Arsić, A., Yu, C., Messelodi, D., Oldrati, M., Schöndorf, D. C., Maria Jose Perez, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18755-4 · Cited by 130 · see citing works
The heterogeneity of Parkinson’s disease
Wüllner, U., Borghammer, P., Choe, C., Csóti, I., Falkenburger, B. H., Gasser, T., Lingor, P., & Riederer, P. F. (2023) · Journal of Neural Transmission · doi:10.1007/s00702-023-02635-4 · Cited by 132 · see citing works
Wang, P., Yao, L., Luo, M., Zhou, W., Jin, X., Xu, Z., Shi, Y., Li, Y., Xu, C., Cheng, R., et al. (2021) · Cell Discovery · doi:10.1038/s41421-021-00280-3 · Cited by 124 · see citing works
The Gut-Brain Axis in Inflammatory Bowel Disease—Current and Future Perspectives
Günther, C., Rothhammer, V., Karow, M., Neurath, M., & Winner, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168870 · Cited by 123 · see citing works
Self-citationSubbarayan, M. S., Hudson, C., Moss, L. D., Nash, K. R., & Bickford, P. C. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01911-4 · Cited by 107 · see citing works
α-Synuclein in Parkinson’s disease: causal or bystander?
Riederer, P. F., Berg, D., Casadei, N., Cheng, F., Claßen, J., Dresel, C., Jost, W. H., Krüger, R., Müller, T. H., Reichmann, H., et al. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-019-02025-9 · Cited by 118 · see citing works
Self-citationInsights into T‐cell dysfunction in Alzheimer's disease
Dai, L., & Shen, Y. (2021) · Aging Cell · doi:10.1111/acel.13511 · Cited by 119 · see citing works
Innate and adaptive immune responses in Parkinson's disease
Schonhoff, A. M., Williams, G. P., Wallen, Z. D., Standaert, D. G., & Harms, A. S. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.10.006 · Cited by 115 · see citing works
Neurodegeneration by α-synuclein-specific T cells in AAV-A53T-α-synuclein Parkinson’s disease mice
Karikari, A. A., McFleder, R. L., Ribechini, E., Blum, R., Bruttel, V., Knorr, S., Gehmeyr, M., Volkmann, J., Brotchie, J. M., Ahsan, F., et al. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2022.01.007 · Cited by 116 · see citing works
Gut microbiome and Parkinson's disease: Perspective on pathogenesis and treatment
Salim, S., Ahmad, F. A., Banu, A., & Mohammad, F. (2022) · Journal of Advanced Research · doi:10.1016/j.jare.2022.10.013 · Cited by 120 · see citing works
Patrick, K. L., Bell, S. L., Weindel, C. G., & Watson, R. O. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00138 · Cited by 110 · see citing works
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Apodaca, L. A., Baddour, A. A. D., Garcia, C., Alikhani, L., Giedzinski, E., Ru, N., Agrawal, A., Acharya, M. M., & Baulch, J. E. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00791-x · Cited by 109 · see citing works
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Kwon, O., Song, J., Yang, Y., Kim, S., Kim, J. Y., Seok, M., Hwang, I., Yu, J., Karmacharya, J., Maeng, H., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013076 · Cited by 110 · see citing works
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Yan, Z., Yang, W., Wei, H., Dean, M. N., Standaert, D. G., Cutter, G., Benveniste, E. N., & Qin, H. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000001036 · Cited by 110 · see citing works
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Shi, Y., Wei, B., Li, L., Wang, B., & Sun, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.932152 · Cited by 108 · see citing works
T cell infiltration in both human multiple system atrophy and a novel mouse model of the disease
Williams, G. P., Marmion, D. J., Schonhoff, A. M., Jurkuvenaite, A., Won, W.-J., Standaert, D. G., Kordower, J. H., & Harms, A. S. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02126-w · Cited by 102 · see citing works
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Immunotherapy for Parkinson’s disease
Schwab, A. D., Thurston, M. J., Machhi, J., Olson, K. E., Namminga, K. L., Gendelman, H. E., & Mosley, R. L. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104760 · Cited by 98 · see citing works
Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases
Ferreira, C., Vieira, P., Sá, H., Malva, J. O., Castelo-Branco, M. S., Reis, F., & Viana, S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1360065 · Cited by 103 · see citing works
Immune responses in the Parkinson's disease brain
Weiss, F. C., Labrador‐Garrido, A., Dzamko, N. L., & Halliday, G. M. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105700 · Cited by 97 · see citing works
Grotemeyer, A., McFleder, R. L., Wu, J., Wischhusen, J., & Ip, C. W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.878771 · Cited by 91 · see citing works
Lee, E. J., Choi, Y., Lee, H. J., Hwang, D. W., & Lee, D. S. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01356-2 · Cited by 89 · see citing works
Neuroinflammatory Responses and Parkinson’ Disease: Pathogenic Mechanisms and Therapeutic Targets
Yang, L., Mao, K., Yu, H., & Chen, J. (2020) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-020-09926-7 · Cited by 90 · see citing works
Xu, Y., Li, Y., Wang, C., Han, T., Liu, H., Sun, L., Hong, J., Hashimoto, M., & Wei, J. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02723-y · Cited by 88 · see citing works
Gut-first Parkinson’s disease is encoded by gut dysbiome
Muñoz, M., Candeias, E., Melo-Marques, I., Esteves, A. R., Maranha, A., Magalhães, J. D., Carneiro, D. R., Sant’Anna, M., Pereira-Santos, A. R., Abreu, A. E., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00766-0 · Cited by 88 · see citing works
Feng, Y.-K., Wu, Q.-L., Peng, Y.-W., Liang, F.-Y., You, H.-J., Feng, Y.-W., Li, G., Li, X.-J., Liu, S.-H., Li, Y.-C., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02027-5 · Cited by 87 · see citing works
Kip, E., & Parr‐Brownlie, L. C. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101618 · Cited by 88 · see citing works
Schulze, M., Sommer, A., Plötz, S., Farrell, M., Winner, B., Grosch, J., Winkler, J., & Riemenschneider, M. J. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0561-x · Cited by 86 · see citing works
Self-citationStorelli, E., Cassina, N., Rasini, E., Marino, F., & Cosentino, M. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00013 · Cited by 84 · see citing works
Green, H. F., Khosousi, S., & Svenningsson, P. (2019) · Journal of Parkinson s Disease · doi:10.3233/jpd-191699 · Cited by 84 · see citing works
Oligodendroglial α‐synucleinopathy‐driven neuroinflammation in multiple system atrophy
Hoffmann, A., Ettle, B., Battis, K., Reiprich, S., Schlachetzki, J. C. M., Masliah, E., Wegner, M., Kuhlmann, T., Riemenschneider, M. J., & Winkler, J. (2019) · Brain Pathology · doi:10.1111/bpa.12678 · Cited by 83 · see citing works
Self-citationGuo, B., Zhang, J., Zhang, W., Chen, F., & Liu, B. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2272769 · Cited by 84 · see citing works
Thome, A. D., Atassi, F., Wang, J., Faridar, A., Zhao, W., Thonhoff, J. R., Beers, D. R., Lai, E. C., & Appel, S. H. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00188-5 · Cited by 79 · see citing works
Duan, W.-X., Wang, F., Liu, J., & Liu, C. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01123-9 · Cited by 78 · see citing works
Wu, Y., Chiu, F., Yeh, C.-S., & Kuo, H. (2019) · Open Biology · doi:10.1098/rsob.180177 · Cited by 75 · see citing works
Neuroinflammation in Parkinson’s Disease: Triggers, Mechanisms, and Immunotherapies
Wang, T., Shi, C., Luo, H., Zheng, H., Fan, L., Tang, M., Su, Y., Yang, J., Mao, C., & Xu, Y. (2021) · The Neuroscientist · doi:10.1177/1073858421991066 · Cited by 66 · see citing works
Unique signatures of stress-induced senescent human astrocytes
Simmnacher, K., Krach, F., Schneider, Y., Alecu, J. E., Mautner, L., Klein, P., Roybon, L., Prots, I., Xiang, W., & Winner, B. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113466 · Cited by 63 · see citing works
Self-citationBrain and Systemic Inflammation in De Novo Parkinson's Disease
Yacoubian, T. A., Fang, Y.-H. D., Gerstenecker, A. T., Amara, A. W., Stover, N. P., Ruffrage, L., Collette, C., Kennedy, R., Zhang, Y., Hong, H., et al. (2023) · Movement Disorders · doi:10.1002/mds.29363 · Cited by 63 · see citing works
Liu, S.-Y., Qiao, H.-W., Song, T.-B., Liu, X.-L., Yao, Y.-X., Zhao, C.-S., Barret, O., Xu, S.-L., Cai, Y.-N., Tamagnan, G. D., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02574-z · Cited by 62 · see citing works
T-cell dysregulation is associated with disease severity in Parkinson’s Disease
Bhatia, D., Grozdanov, V., Ruf, W. P., Kassubek, J., Ludolph, A. C., Weishaupt, J. H., & Danzer, K. M. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02296-8 · Cited by 62 · see citing works
T Lymphocytes in Parkinson’s Disease
Contaldi, E., Magistrelli, L., & Comi, C. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223152 · Cited by 62 · see citing works
Pons‐Espinal, M., Blasco-Agell, L., Fernández‐Carasa, I., Andrés‐Benito, P., di Domenico, A., Richaud‐Patín, Y., Baruffi, V., Marruecos, L., Espinosa, L., Garrido, A., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.163359 · Cited by 66 · see citing works
The systemic immune response in Parkinson’s disease: focus on the peripheral immune component
Lauritsen, J., & Romero‐Ramos, M. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.07.005 · Cited by 64 · see citing works
Roles for the adaptive immune system in Parkinson’s and Alzheimer’s diseases
Arlehamn, C. S. L., Garretti, F., Sulzer, D. L., & Sette, A. (2019) · Current Opinion in Immunology · doi:10.1016/j.coi.2019.07.004 · Cited by 61 · see citing works
Association Between Parkinson’s Disease and Melanoma: Putting the Pieces Together
Ye, Q., Wen, Y., Al-Kuwari, N., & Chen, X. M. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00060 · Cited by 60 · see citing works
Neuroinflammation and Immune Changes in Prodromal Parkinson’s Disease and Other Synucleinopathies
Terkelsen, M. H., Klæstrup, I. H., Hvingelby, V. S., Lauritsen, J., Pavese, N., & Romero‐Ramos, M. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223245 · Cited by 63 · see citing works
Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria
Esteves, A. R., Muñoz, M., Nunes‐Costa, D., Candeias, E., Silva, D. F., Magalhães, J. D., Pereira-Santos, A. R., Ferreira, I. L., Alarico, S., Tiago, I., et al. (2021) · Gut · doi:10.1136/gutjnl-2021-326023 · Cited by 61 · see citing works
Garretti, F., Monahan, C., Sloan, N., Bergen, J., Shahriar, S., Kim, S. W., Sette, A., Cutforth, T., Kanter, E., Agalliu, D., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.07.015 · Cited by 59 · see citing works
Central and Peripheral Inflammation: Connecting the Immune Responses of Parkinson’s Disease
Williams, G. P., Schonhoff, A. M., Sette, A., & Arlehamn, C. S. L. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223241 · Cited by 61 · see citing works
The Influence of Virus Infection on Microglia and Accelerated Brain Aging
Filgueira, L., Larionov, A. A., & Lannes, N. (2021) · Cells · doi:10.3390/cells10071836 · Cited by 57 · see citing works
Abnormal B-Cell and Tfh-Cell Profiles in Patients With Parkinson Disease
Li, R., Tropea, T. F., Baratta, L. R., Zuroff, L. R., Diaz‐Ortiz, M. E., Zhang, B., Shinoda, K., Rezk, A., Alcalay, R. N., Chen‐Plotkin, A. S., et al. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000001125 · Cited by 57 · see citing works
Li, D., Mastaglia, F. L., Fletcher, S., & Wilton, S. D. (2020) · Medicinal Research Reviews · doi:10.1002/med.21718 · Cited by 57 · see citing works
Li, X., Koudstaal, W., Fletcher, L., Costa, M., van Winsen, M., Siregar, B., Inganäs, H., Kim, J., Keogh, E. A., Macedo, J., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01974-5 · Cited by 54 · see citing works
Liang, B., Deng, Y., Huang, Y., Zhong, Y., Li, Z., Du, J., Ye, R., Feng, Y., Bai, R., Fan, B., et al. (2024) · ACS Nano · doi:10.1021/acsnano.4c03874 · Cited by 53 · see citing works
Pro-survival and anti-inflammatory roles of NF-κB c-Rel in the Parkinson's disease models
Wang, Z., Dong, H., Wang, J., Huang, Y., Zhang, X., Tang, Y., Li, Q., Liu, Z., Ma, Y., Tong, J., et al. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101427 · Cited by 52 · see citing works
Th17 Cells and IL-17A in Ischemic Stroke
Wang, J., Gao, Y., Yuan, Y., Wang, H., Wang, Z., & Zhang, X. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03723-y · Cited by 53 · see citing works
Arias, C., Sepúlveda, P., Castillo, R. L., & Salazar, L. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043073 · Cited by 50 · see citing works
Neuroinflammation in Parkinson’s Disease: From Gene to Clinic: A Systematic Review
Castillo-Rangel, C., Marín, G., Hernández-Contreras, K. A., Vichi-Ramírez, M. M., Zarate-Calderon, C., Torres-Pineda, O., Díaz-Chiguer, D. L., González, D. D. L. M., Apo, E. G., Teco-Cortes, J. A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065792 · Cited by 49 · see citing works
Kumar, P., Chan, D. W. S., Lim, A. J. M., Paleja, B. S., Ling, S. R., Yun, L. L., Poh, S. L., Ngoh, A. S. F., Arkachaisri, T., Yeo, J. G., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.126337 · Cited by 48 · see citing works
Ostendorf, F., Metzdorf, J., Gold, R., Haghikia, A., & Tönges, L. (2020) · Molecules · doi:10.3390/molecules25112502 · Cited by 46 · see citing works
Li, J., Zhao, J., Chen, L., Gao, H., Zhang, J., Wang, D., Zou, Y., Qin, Q., Qu, Y., Li, J., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.10.023 · Cited by 48 · see citing works
Zhuo, Y., Li, W., Lu, W. Q., Li, X., Ge, L., Huang, Y., Gao, Q., Deng, Y.-J., Jiang, X., Lan, Z.-W., et al. (2024) · Military Medical Research · doi:10.1186/s40779-024-00550-7 · Cited by 52 · see citing works
Domínguez-Fernández, C., Egiguren-Ortiz, J., Razquin, J., Gómez-Galán, M., Heras-García, L. D. L., Paredes-Rodriguez, E., Astigarraga, E., Miguélez, C., & Barreda‐Gómez, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043321 · Cited by 49 · see citing works
Role of mtDNA disturbances in the pathogenesis of Alzheimer’s and Parkinson’s disease
Antonyová, V., Kejík, Z., Brogyányi, T., Kaplánek, R., Pajková, M., Talianová, V., Hromádka, R., Masařík, M., Sýkora, D., Mikšátková, L., et al. (2020) · DNA Repair · doi:10.1016/j.dnarep.2020.102871 · Cited by 45 · see citing works
IL-17A injury to retinal ganglion cells is mediated by retinal Müller cells in diabetic retinopathy
Qiu, A.-W., Huang, D., Li, B., Fang, Y., Zhang, W., & Liu, Q.-H. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04350-y · Cited by 44 · see citing works
Grotemeyer, A., Fischer, J. F., Koprich, J. B., Brotchie, J. M., Blum, R., Volkmann, J., & Ip, C. W. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02759-0 · Cited by 44 · see citing works
Greenland, J. C., Cutting, E., Kadyan, S., Bond, S. J., Chhabra, A., & Williams‐Gray, C. H. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-040527 · Cited by 43 · see citing works
CD4 + T‐cell Transcription Factors in Idiopathic REM Sleep Behavior Disorder and Parkinson's Disease
Francesco, E. D., Terzaghi, M., Storelli, E., Magistrelli, L., Comi, C., Legnaro, M., Mauri, M. F., Marino, F., Versino, M., & Cosentino, M. (2020) · Movement Disorders · doi:10.1002/mds.28137 · Cited by 42 · see citing works
Kerkering, J., Muinjonov, B., Rosiewicz, K., Diecke, S., Biese, C., Schiweck, J., Chien, C., Zocholl, D., Conrad, T., Paul, F., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci164637 · Cited by 32 · see citing works
The Role of IL-17A in Mediating Inflammatory Responses and Progression of Neurodegenerative Diseases
Zheng, M., & Luo, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062505 · Cited by 43 · see citing works
- Authors
- Sommer, A., Marxreiter, F., Krach, F., Fadler, T., Grosch, J., Maroni, M., Graef, D., Eberhardt, E., Riemenschneider, M. J., Yeo, G. W., Kohl, Z., Xiang, W., Gage, F. H., Winkler, J., Prots, I., & Winner, B.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University Hospital Regensburg (DE)
- University of California San Diego (US)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Prots, Iryna
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 23
- Issue
- 1
- Pages
- 123-131.e6
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2868920275
- Cited by
- 332
- References
- 39
- Citations by year
- 2026: 29 · 2025: 38 · 2024: 43 · 2023: 48 · 2022: 46 · 2021: 45 · 2020: 54 · 2019: 21 · 2018: 8
- FWCI
- 21.90
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-06-06)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- JPB Foundation
- Nederlandse Hersenbank (NBB #1043)
- Deutsche Forschungsgemeinschaft (410/45-1 FUGG, GRK2162)
- Bundesministerium für Bildung und Forschung (01EK1609B, 01GM1520A, 01GQ113)
- Bayerisch-Kalifornischen Hochschulzentrum
- G. Harold and Leila Y. Mathers Charitable Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, Th17 cells, IL-17, IL-17 receptor, NF-κB signaling, neuronal cell death, adaptive immune response, secukinumab, sporadic Parkinson's disease, neuroinflammation
- MeSH terms
- Cells, Cultured, Female, Humans, Male, Models, Biological, Neurons, Parkinson Disease, Cell Death, Induced Pluripotent Stem Cells, Th17 Cells
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