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The Glia-Derived Alarmin IL-33 Orchestrates the Immune Response and Promotes Recovery following CNS Injury
Open accessAbstract
Inflammation is a prominent feature of CNS injury that heavily influences neuronal survival, yet the signals that initiate and control it remain poorly understood. Here we identify the nuclear alarmin, interleukin (IL)-33, as an important regulator of the innate immune response after CNS injury. IL-33 is expressed widely throughout the healthy brain and is concentrated in white mater due to predominant expression in post-mitotic oligodendrocytes. IL-33 is released immediately after CNS injury from damaged oligodendrocytes, acting on local astrocytes and microglia to induce chemokines critical for monocyte recruitment. Mice lacking IL-33 have impaired recovery after CNS injury, which is associated with reduced myeloid cell infiltrates and decreased induction of M2 genes at the injury site. These results demonstrate a novel molecular mediator contributing to immune cell recruitment to the injured CNS and may lead to new therapeutic insights in CNS injury and neurodegenerative diseases.
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“However, recent data indicate that microglia and astrocytes coordinate their functions in many ways, both in the healthy and diseased brain [14–21].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [15]
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Schmitz, J., Owyang, A. M., Oldham, E. R., Song, Y., Murphy, E., McClanahan, T. K., Zurawski, G., Moshrefi, M., Qin, J., Li, X., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.09.015 · Cited by 3,773 · cited 3×
“A potential explanation of these dual aspects is macrophage phenotype, with the alternative (M2) and classical (M1) polarization correlating with beneficial or detrimental responses, respectively (Kigerl et al., 2009; Kroner et al., 2014; Schmitz et al., 2005; Shechter et al., 2009, 2013).”
Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129 · cited 2×
“Costaining of IL-33 with the astrocyte marker ALDH1L1 (Cahoy et al., 2008) demonstrated that these cells were astrocytes, which express IL-33 in gray matter regions (i.e., neocortex) but not in white matter (i.e., corpus callosum ; Figures 1F and 1G).”
Kigerl, K. A., Gensel, J. C., Ankeny, D. P., Alexander, J. K., Donnelly, D. J., & Popovich, P. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3257-09.2009 · Cited by 2,130 · cited 2×
“A potential explanation of these dual aspects is macrophage phenotype, with the alternative (M2) and classical (M1) polarization correlating with beneficial or detrimental responses , respectively (Kigerl et al., 2009; Kroner et al., 2014; Schmitz et al., 2005; Shechter et al., 2009, 2013).”
Basso, D., Fisher, L., Anderson, A., Jakeman, L., McTigue, D. M., & Popovich, P. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.635 · Cited by 1,615 · cited 2×
“Error bars represent mean ± SEM; *p % 0.05; **p % 0.01; ***p % 0.001. relative to WT counterparts after SCI, as assessed by Basso mouse scale (Basso et al., 2006 ) (Figure 3E).”
InfluentialDisease-associated functions of IL-33: the new kid in the IL-1 family
Liew, F. Y., Pitman, N. I., & McInnes, I. B. (2010) · Nature reviews. Immunology · doi:10.1038/nri2692 · Cited by 1,020 · cited 2×
“Interleukin (IL)-33 is a nuclear alarmin of the IL-1 cytokine family released by cell damage and is well characterized as an immune activator in conditions such as asthma (Liew et al., 2010), allergy (Oboki et al., 2010), and sepsis (Alves-Filho et al., 2010).”
Neuronal and Glial Apoptosis after Traumatic Spinal Cord Injury
Liu, X. Z., Xu, X. M., Hu, R., Du, C., Zhang, S. X., McDonald, J. W., Dong, H. X., Wu, Y. J., Fan, G. S., Jacquin, M. F., et al. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-14-05395.1997 · Cited by 770 · cited 1×
“Neurons and glia directly damaged by the initial insult die, both necrotically and apoptotically (Grossman et al., 2001; Liu et al., 1997; Lytle and Wrathall, 2007), followed by secondary degeneration—a spread of damage through apoptotic death of initially uninjured neurons (Dusart and Schwab,…”
Shechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., Martino, G., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000113 · Cited by 770 · cited 1×
“A potential explanation of these dual aspects is macrophage phenotype, with the alternative (M2) and classical (M1) polarization correlating with beneficial or detrimental responses, respectively (Kigerl et al., 2009; Kroner et al., 2014; Schmitz et al., 2005; Shechter et al., 2009, 2013).”
BackgroundKurowska‐Stolarska, M., Stolarski, B., Kewin, P., Murphy, G., Corrigan, C. J., Ying, S., Pitman, N. I., Mirchandani, A. S., Rana, B. M. J., van Rooijen, N., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901575 · Cited by 747 · cited 1×
“Given previous reports showing that IL-33 can polarize toward an ‘‘M2’’ (IL-4-activated) macrophage skew (Kurowska-Stolarska et al., 2009) and that M2 macrophages promote neuronal survival (Kigerl et al.”
BackgroundShechter, R., Miller, O., Yovel, G., Rosenzweig, N., London, A., Ruckh, J., Kim, K.-W., Klein, E., Kalchenko, V., Bendel, P., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.012 · Cited by 683 · cited 2×
“The overall impact of this immune response remains debated, as it has potential to drive both beneficial (Shechter et al., 2013; Walsh et al., 2015; Walsh et al., 2014) and detrimental (Evans et al., 2014; Kroner et al., 2014) effects on recovery.”
Suppression of Interleukin-33 Bioactivity through Proteolysis by Apoptotic Caspases
Lüthi, A. U., Cullen, S. P., McNeela, E. A., Duriez, P. J., Afonina, I. S., Sheridan, C., Brumatti, G., Taylor, R. C., Kersse, K., Vandenabeele, P., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.007 · Cited by 677 · cited 1×
“Upon release from necrotically dying cells (Lüthi et al., 2009), IL-33 binds IL-33R, a heterodimer of IL-1RAcP and ST2, and initiates an intracellular cascade involving MyD88 and NFkB (Liew et al.”
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- Levkovitch-Verbin, 2000, RGC death in mice after optic nerve crush injury: oxidative stress and neuroprotection, Invest. Ophthalmol. Vis. Sci., 41, 4169
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Items 201–300 of 321
IL-33 promotes sciatic nerve regeneration in mice by modulating macrophage polarization
Smail, S. W., Abdulqadir, S. Z., Khudhur, Z. O., Ishaq, S. E., Ahmed, A. F., Ghayour, M. B., & Abdolmaleki, A. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110711 · Cited by 14
Natural Products for Regulating Macrophages M2 Polarization
Chang, Z., Wang, Y., Liu, C., Smith, W. W., & Kong, L. (2019) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x14666190523093535 · Cited by 17
Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury
Anderson, K. M., Welsh, C. J., Young, C., Levine, G., Kerwin, S., Boudreau, C., Reyes, I., Mondragon, A., Griffin, J. F., Cohen, N., et al. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2015.3895 · Cited by 14
“from rodent contusion models suggest the presence of early proand anti-inflammatory signaling in SCI, which may be augmented by polarization of macrophages to M1 and M2 phenotypes, respectively.(41,42)”
Stem cells in skeletal muscle growth and regeneration in amniotes and teleosts: Emerging themes
Ruparelia, A. A., Ratnayake, D., & Currie, P. D. (2019) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.365 · Cited by 15
Cross-regulation between the nervous system and type 2 immunity
Mroz, N. M., Chiaranunt, P., Molofsky, A. V., & Molofsky, A. B. (2025) · Science Immunology · doi:10.1126/sciimmunol.adp6450 · Cited by 12
Oligodendrocyte-derived IL-33 regulates self-reactive CD8+ T cells in CNS autoimmunity
Fonta, N., Pagé, N., Klimek, B., Piccinno, M., Liberto, G. D., Lemeille, S., Kreutzfeldt, M., Kastner, A. L., Ertuna, Y. I., Vincenti, I., et al. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20241188 · Cited by 13
“The primary sources of IL-33 in the CNS are astrocytes during development (Vainchtein et al., 2018) and oligodendrocytes in adulthood (Gadani et al., 2015).”
InfluentialUnravelling the therapeutic potential of IL-33 for atrophic AMD
Clare, A. J., Liu, J., Copland, D. A., Theodoropoulou, S., & Dick, A. D. (2021) · Eye · doi:10.1038/s41433-021-01725-5 · Cited by 12
Gupta, S., Adhikary, S., & Hui, S. P. (2021) · Clinical & Experimental Immunology · doi:10.1111/cei.13661 · Cited by 12
“In the central nervous system (CNS), IL- 33 recruits Tregs to perform a reparative function by promoting M2 macrophage polarization to aid remyelination and oligodendrocyte differentiation [35].”
BackgroundThe essential function of IL-33 in metabolic regulation
Li, W., Li, Y., & Jin, J. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa045 · Cited by 12
Zeng, C., Sheu, J., & Tsai, H. (2020) · Cell Transplantation · doi:10.1177/0963689720903679 · Cited by 12
“Gadani et al.30 reported that repair mechanisms rely on beneficial aspects of inflammation in mammals.”
BackgroundBarbour, M., Wood, R., Hridi, S. U., Wilson, C., McKay, G., Bushell, T. J., & Jiang, H. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.02.012 · Cited by 11
“In addition, IL-33 promotes recovery after CNS injury in mice (Gadani et al., 2015) and ST2 deficient mice display increased susceptibility to viral-induced encephalitis (Franca et al.”
Xu, Y., Zhao, J., Xu, X., Liu, Y., Li, Y., & Peng, L. (2026) · Small · doi:10.1002/smll.202513394 · Cited by 11
Tan, Y. J., Siow, I., Saffari, S. E., Ting, S. K. S., Zeng, L., Kandiah, N., Tan, L. C. S., Tan, E., & Ng, A. S. L. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221072 · Cited by 14
Perturbations to Homeostasis in Experimental Models Revealed Innate Pathways Driving Food Allergy
Bruton, K. M., Koenig, J. F. E., Phelps, A., & Jordana, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.603272 · Cited by 15
“To date, components of this pathway have been implicated in homeostatic maintenance in the skin (18, 19), muscles (9, 20), intestines (27, 28), nervous system (29, 30), liver (8, 31, 32), biliary tract (15), lungs (16), kidney (11), adipose tissue (33), among others.”
BackgroundDu, J.-J., Liu, Z.-Q., Yan, Y., Xiong, J., Jia, X.-T., Di, Z., & Ren, J.-J. (2019) · Journal of Molecular Neuroscience · doi:10.1007/s12031-019-01429-2 · Cited by 11
Wu, Z., Zhai, M., Wang, Y., Ren, L., Pan, J., Xiao, L., & Liu, Y. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107117 · Cited by 13
García-Vicente, L., Martínez-Fernández, M., Borja, M., Tran, V., Álvarez-Vázquez, A., Flores-Hernández, R., Ding, Y., González-Sánchez, R., Granados, A. A., McGeever, A., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08092-x · Cited by 15
“Oligo-dendrocytesshowedstrikinglyhighexpressionof Il33 ,whichisknowntobe released upon CNS injury as an alarmin that acts on local astrocytes and microglia to induce chemokines for monocyte recruitment 61 , while being implicated in oligodendrocyte maturation 62 .”
Shang, T., Kuang, B., Shang, Y., & Zou, W. (2025) · Current Neuropharmacology · doi:10.2174/011570159x350639250403072430 · Cited by 12
“CNS injuries can trigger damaged brain cells to release IL-33, primarily produced by oligodendrocytes and astrocytes [163, 164], while ST2 mainly colocalizes with microglia [165].”
The neuroimmune mechanism of pain induced depression in psoriatic arthritis and future directions
Wang, X., Wu, L., Liu, J., Ma, C., Liu, J., & Zhang, Q. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117802 · Cited by 12
Norris, G. T., Ames, J. M., Ziegler, S. F., & Oberst, A. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011350 · Cited by 13
Zhu, Y., Yao, H., Lu, H.-Y., Hao, X., & Xu, S. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17654 · Cited by 10
The IL-33/ST2 Pathway in Cerebral Malaria
Glineur, C., Leleu, I., & Pied, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113457 · Cited by 11
“Around 33% of isolated brain cells of naïve mice are IL-33-positive [65,66] and IL-33 mRNA expression level is higher in the brain than in any other tissues and organs tested [25].”
BackgroundSanford, L. D., Wellman, L. L., Ciavarra, R. P., Oldfield, E. C., Shams, R., Copare, J., & Johnson, D. A. (2021) · Life · doi:10.3390/life11121283 · Cited by 9
“chemokines that recruit monocytes that promote expression of reparatory M2 macrophage genes, and appears o be important for CNS recovery after injury [41].”
BackgroundInfluentialMado, H., Adamczyk-Sowa, M., Bartman, W., Wierzbicki, K., Tadeusiak, B., & Sowa, P. (2021) · Clinical neurology and neurosurgery (Dutch-Flemish ed. Print) · doi:10.1016/j.clineuro.2021.106700 · Cited by 10
“IL-33 as an alarmin could be released in response to tissue damage-demyelination and through its effect on oligodendrocytes stimulate remyelination and, as a result, its high plasma levels would protect against the development of MRI-visible lesions consistent with demyelination [25,26,33].”
BackgroundTemporospatial Analysis and New Players in the Immunology of Amyotrophic Lateral Sclerosis
Iyer, A. K., Jones, K. J., Sanders, V. M., & Walker, C. L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020631 · Cited by 11
“In another study, IL-33 released by oligodendrocytes and astrocytes after CNS injury works with yet-to-be identified factors to steer macrophages towards an anti-inflammatory, pro-regenerative M2 phenotype [91].”
BackgroundThe role of gut microbiota in neuropathic pain: insights into immune mechanisms
Gong, Z., Zou, J., Fang, Y., Li, J., Luo, Y., Xue, Q., Yu, B., Hua, B., & Liu, Z. (2025) · The Journal of Headache and Pain · doi:10.1186/s10194-025-02260-4 · Cited by 10
Critical and diverse role of alarmin cytokines in parasitic infections
Xing, Z., Liu, S., & He, X. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1418500 · Cited by 10
“In humans and mice, IL-33 is constitutively expressed at high levels within the brain, particularly in stromal cells such as astrocytes and oligodendrocytes (Gadani et al., 2015; Abd Rachman Isnadi et al., 2018).”
More Attention on Segments Remote from the Primary Spinal Cord Lesion Site
Chelyshev, Y. A. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2708235 · Cited by 12
“Another nuclear alarmin, IL-33, which is expressed in gray matter oligodendrocytes and astrocytes, is released from injured tissue, appears in CSF, and drives chemokine production critical for monocyte recruitment after SCI [118].”
BackgroundRole of Interleukin1 receptor-like 1 (ST2) in cerebrovascular disease
Sastre, C., Bevers, M., & Kimberly, W. (2021) · Neurocritical Care · doi:10.1007/s12028-021-01284-3 · Cited by 9
“Within the brain, IL-33 is expressed in postmitotic Oligodendrocyte Transcription Factor 2 (OLIG2 +) oligodendrocytes [24].”
BackgroundInfluentialResolution of inflammation and repair after ischemic brain injury
Yoshimura, A., & Ito, M. (2020) · doi:10.20517/2347-8659.2020.22 · Cited by 9
“IL-33 Of note, IL-33 promotes tissue recovery after CNS injury([81]) and up-regulates M2 type macrophage-related genes([82]).”
BackgroundBorghi, S. M., de Carvalho, T. T., Bertozzi, M. M., Bernardy, C. C. F., Zarpelon, A. C., Pinho-Ribeiro, F. A., Calixto-Campos, C., Fattori, V., Alves-Filho, J. C., Cunha, T. M., et al. (2025) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2025.111476 · Cited by 8
Qian, Z., Jiao, M., Zhang, N., Tang, X., Liu, S., Zhang, F., Wang, C., & Zheng, F. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-024-01279-y · Cited by 8
“Some studies have reported the neuroprotective effects of exogenous IL-33 in animal models of CNS injury [18, 23, 61].”
Positive selection of IL ‐33 in adaptive immunity of domestic Chinese goats
Asif, A. R., Awais, M., Qadri, S., Ahmad, H. I., & Du, X. (2017) · Ecology and Evolution · doi:10.1002/ece3.2813 · Cited by 9
“, 2013), disorders of the central nervous system (Gadani et al., 2015), TABLE 4 Maximum likelihood analysis of natural selection codon by codon”
BackgroundKilgore, M. D., Xiu, Y., Jiang, Y., Wang, Y., Shi, M., Zhou, D., Sein, T. Y., Vodovoz, S. J., Wang, D., Dumont, A. S., et al. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70580 · Cited by 7
“This function is augmented via the alarmin IL-33, which has recently been highlighted as an early immune signal released from damaged neurons and glia in acute brain injury [66, 67].”
Tobori, S., Tamada, K., Uemura, N., Sawada, K., Kakae, M., Nagayasu, K., Nakagawa, T., Mori, Y., Kaneko, S., & Shirakawa, H. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2416828122 · Cited by 8
“Oligodendrocytes lineage cells (OLs) are implicated in neuropathic pain; after peripheral nerve injury, spinal OLs produce interleukin - 33 (IL33), which activates microglia and promotes the development of neuropathic pain (44, 45).”
Stepwise acquisition of unique epigenetic signatures during differentiation of tissue Treg cells
Braband, K. L., Kaufmann, T., Floess, S., Zou, M., Huehn, J., & Delacher, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1082055 · Cited by 10
“Indeed, the accumulation of brain Treg cells potentiates neurological recovery during the chronic phase of ischemic brain injury (43, 44).”
BackgroundMai, E., Chan, J. H. S., Goon, L., Ego, B. K., Bevers, J. J., Wong, T., Wong, M., Corpuz, R. T., Xi, H., Wu, J., et al. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-03189-3 · Cited by 9
“It has an elevated constitutive expression in endothelial cells, epithelial cells and fibroblast-like cells [18] and its expression can be further increased during inflammation [10, 19, 20].”
BackgroundGlial PAMPering and DAMPening of Adult Hippocampal Neurogenesis
Parkitny, L., & Maletić‐Savatić, M. (2021) · Brain Sciences · doi:10.3390/brainsci11101299 · Cited by 9
Therapeutic Potential of Cytokines in Demyelinating Lesions After Stroke
Guo, Y., Yuan, M., Han, Y., Shen, X.-Y., Gao, Z.-K., & Bi, X. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01851-5 · Cited by 8
Clare, A. J., Copland, D. A., Nicholson, L. B., Liu, J., Neal, C., Moss, S. E., Dick, A. D., & Theodoropoulou, S. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16000 · Cited by 7
Anti-inflammatory effects of rice bran components
Kurtys, E., Eisel, U. L. M., Hageman, R. J. J., Verkuyl, J. M., Broersen, L. M., Dierckx, R., & de Vries, E. F. J. (2018) · Nutrition Reviews · doi:10.1093/nutrit/nuy011 · Cited by 20
IL-33 Deals with the Gray Matter
Delmas, C., & Dalmas, É. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.005 · Cited by 9
Brain Endothelial Soluble ST2 Production and Cerebral Edema in a Rat Model of Ischemic Stroke
Bevers, M. B., An, J., Yoo, A., Fietsam, E., Booraem, C., Reddy, D., Li, K., Sastre, C., Acharjee, A., Sugimoto, K., et al. (2025) · Annals of Neurology · doi:10.1002/ana.78006 · Cited by 4
“18 In the current study, we sought to fi rst verify the relationship between sST2 and brain swelling in a cohort of acute stroke patients with large hemispheric stroke.”
Mitchener, V. F. T., Thackray, M. J., & Arancibia‐Cárcamo, I. L. (2025) · The Journal of Physiology · doi:10.1113/jp287015 · Cited by 8
“Generally these cytokines are considered to have positive effects on myelination, promoting myelin maintenance and repair (Gadani et al., 2015; Zhang et al., 2006).”
Huang, H.-T., & Tzeng, S. (2023) · Neurochemistry International · doi:10.1016/j.neuint.2023.105645 · Cited by 7
Tian, J., Zhu, J., Fan, Q., Luo, X., Nie, Q., Yu, J., Wu, X., Tang, Y., Liu, T., & Yin, H. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110778 · Cited by 7
Robin, A., Mackowiak, C., Bost, R., Dujardin, F., Barbarin, A., Thierry, A., Hauet, T., Pellerin, L., Gombert, J., Salamé, E., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1099529 · Cited by 7
“For qualitative evaluation (CD69 and CD4 expression), iNKT cells could be counted (mean ± SEM and range/sample) in all HS (387 ± 148 [30-4221]), and in 8 (out of 17) (127 ± 51 [13-399]) and 9 (out of 16) (40 ± 17 [10-2982]) patients before and at the end of LT, respectively.”
BackgroundWang, M., Xia, D., Sun, L., Bi, J., Xie, K.-Q., & Wang, P. (2023) · European Neurology · doi:10.1159/000530437 · Cited by 6
de Castro, M. V., Silva, M. V. R., Chiarotto, G. B., Santana, M. H. A., Luzo, Â. C. M., Kyrylenko, S., & de Oliveira, A. L. R. (2020) · Stem Cells International · doi:10.1155/2020/8834360 · Cited by 11
“In addition to the extensive degeneration of primary afferent fibers that enter the spinal cord through the dorsal root, a rapid inflammatory reaction characterized by the proliferation, recruitment, and activation of cells of the nervous tissue and the immune system occurs in response to lesions [7].”
BackgroundRao, U. K., & Engelhardt, B. G. (2020) · Clinical Hematology International · doi:10.2991/chi.d.200506.002 · Cited by 6
“Epithelial cells in barrier tissues exposed to the environment, fibroblastic reticular cells in lymphoid organs, and central nervous system glial cells are major sources of IL-33 [18,19,21,22].”
BackgroundMitrokhin, V. M., Kamkin, A. G., Babkina, I., Savinkova, I. G., Shileiko, S. A., Сергеевич, О. Р., & Mladenov, M. I. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27062603 · Cited by 5
“These mediators further enhance BBB permeability, resulting in neurovascular dysfunction (Table 2), [91].”
Cytokine and Chemokine Profiles in Anti-LGI1 Encephalitis
Muñoz‐Sánchez, G., Guasp, M., Lopetegi, A. M., Luchoro, J. F., Martínez‐Hernández, E., Naranjo, L., Erro, M. E., Martín-Aguilar, L., Iizuka, T., Simabukuro, M. M., et al. (2025) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000200492 · Cited by 9
“11 12-17 Furthermore, cytokines and chemokines are also involved in tissue repair and resolution of in fl ammation in the CNS. 18,19 These mediators have been extensively studied in multiple sclerosis 20-22 other autoimmune encephalitides, 23-25 and neuromyelitis optica spectrum disorder (NMOSD), 26…”
Shen, C., Liu, Z., Chen, F., Zhu, X., Fan, G., Ning, P., Li, Q., Zhang, X., Dong, H., Liu, Y., et al. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.07.010 · Cited by 6
Do astrocytes act as immune cells after pediatric TBI?
Panchenko, P. E., Hippauf, L., Konsman, J. P., & Badaut, J. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106231 · Cited by 9
“For example, nuclear alarmin IL-33 is released from damaged oligodendrocytes in white matter and in grey matter astrocytes at 1 day following spinal cord injury (Gadani et al., 2015).”
Chatterton, C. G., Romero, R. J., Jung, E., Gallo, D. M., Suksai, M., Primera, R. J. D., Erez, O., Chaemsaithong, P., Tarca, A. L., Gotsch, F., et al. (2023) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2023.2183470 · Cited by 7
Role of IL-33 in transplant biology
Jin, Y., Kong, D., Liu, C., & Gong, W. (2019) · European Cytokine Network · doi:10.1684/ecn.2019.0429 · Cited by 5
Longitudinal changes in the expression of IL-33 and IL-33 regulated genes in relapsing remitting MS
Sriram, S., Shaginurova, G. I., Tossberg, J. T., Natarajan, C., Spurlock, C. F., & Aune, T. M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0208755 · Cited by 6
Guso, E., Lupoli, A., Olivieri, E., Bottoni, A., Gironi, M., Missarelli, D. M., Toosy, A., Rossi, E., & Furlan, R. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.02.047 · Cited by 4
Budina, E., Reda, J. W., Cao, S., Watkins, E. A., Solanki, A., Nguyen, M., Ang, P. S., Medellin, J. E. G., Chun, H.-R., Foley, C., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102231 · Cited by 3
“23,62 IL-33 is also expressed by mature oligodendrocytes and gray matter astrocytes 61,63 and modulates CNS-resident immune and neuronal cell phenotype.”
Xiao, Y., Hao, L., Cao, X., Zhang, Y., Xu, Q., Qin, L., Zhang, Y., Wu, Y., Zhou, H., Wu, M., et al. (2025) · Neuroscience Bulletin · doi:10.1007/s12264-025-01374-8 · Cited by 3
“…cellular damage or activation, endogenous molecules known as damage-associated molecular patterns (DAMPs) are released, including interleukin-33 (IL-33) [7], high mobility group box 1 (HMGB1) [8], extracellular cold-inducible RNA-binding protein, histones, and heat shock proteins, among others [9].”
García-Vicente, L., Borja, M., Tran, V., Álvarez-Vázquez, A., Flores-Hernández, R., Granados, A. A., McGeever, A., Kim, Y.-J., Dorman, L. C., Detweiler, A. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.26.564166 · Cited by 4
“Oligodendrocytes showed strikingly high expression of Il33 , which is known to be released upon CNS injury as an alarmin that acts on local astrocytes and microglia to induce chemokines for monocyte recruitment 60 , while being implicated in oligodendrocyte maturation 61 .”
BackgroundSun, C., Zheng, S., Perry, J. S. A., Norris, G. T., Cheng, M., Kong, F., Skyberg, R. J., Cang, J., Erişir, A., Kipnis, J., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20212476 · Cited by 4
“S5 D), suggesting that mechanisms, as indicated by others, exist throughout development to regulate cellular metabolism and to potentially influence pruning of terminal fields (Gadani et al., 2015; He et al., 2022).”
Self-citationCarvalho, D. B., Díaz‐Amarilla, P., Dapueto, R., Santi, M. D., Duarte, P., Savio, E., Engler, H., Abin‐Carriquiry, J. A., & Arredondo, F. (2023) · Journal of Molecular Neuroscience · doi:10.1007/s12031-023-02105-2 · Cited by 7
“Moreover, it has a role in injury healing and has been found neuroprotective in multiple models by regulating microglia and astrocyte phenotype (Gadani et al. 2015; Fu et al. 2016; Yang et al. 2017; Carlock et al. 2017; Chen et al. 2019c).”
BackgroundAstrocyte-Neuron Crosstalk Through Hedgehog Signaling Mediates Cortical Circuit AssemblyPreprint
Xie, Y., Kuan, A. T., Wang, W., Herbert, Z. T., Mosto, O., Olukoya, O., Adam, M. A., Vu, S., Kim, M., Gómez, N., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.15.204263 · Cited by 2
“Previous research has shown that in the adult mouse CNS, Il33 is mainly expressed by oligodendrocytes (Gadani et al. 2015).”
BackgroundQu, Y., Mao, Z., Wang, D., An, K., Yu, H. Q., Qin, Q., Li, J., Xiong, Y., Min, Z., & Xue, Z. (2026) · Neuroscience Bulletin · doi:10.1007/s12264-025-01566-2 · Cited by 3
“Nota-bly, IL-33 and its receptors are highly expressed in the CNS, where they influence various pathological processes [10].”
Zhao, R., Gao, S.-Q., Wang, X., Li, T., Gao, C.-C., Han, Y., Qiu, J.-Y., Miao, S.-H., Sun, Y., Zheng, X., et al. (2025) · Journal of Neurotrauma · doi:10.1177/08977151251401226 · Cited by 2
“15 Previous research has found that IL-33 can in fl uence homeostatic synaptic plasticity in the adult hippocampus and decrease the induction of anti-in fl ammatory genes of microglia, 16,17 But few precursor factors that affect the function of IL-33 have been identi fi ed.”
Repurposing of Chemokine Antagonists for Combined Phase‐Resolved Spinal Cord Injury Treatment
Belogurov, A. A., Telegin, G. B., Чернов, А. С., Kudriaeva, A. A., Minakov, A. N., Rodionov, M. V., Kazakov, V. A., Паликов, В. А., Poluektov, Y. M., Ziganshin, R., et al. (2025) · Advanced Science · doi:10.1002/advs.202516569 · Cited by 2
Rajkovic, C. J., MacElroy, D., Spirollari, E., Vazquez, S. M., Subah, G., Lazzari, J. L., Zeller, S. L., Wainwright, J. V., Jhanwar‐Uniyal, M., & Kinon, M. D. (2025) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2025.104011 · Cited by 3
Naef, P., Jaeger-Ruckstuhl, C. A., Schnüriger, N., Forster, S., Monteiro, I., Brigger, D., Eggel, A., Kessenbrock, K., Riether, C., & Ochsenbein, A. F. (2025) · iScience · doi:10.1016/j.isci.2025.112378 · Cited by 5
“63,64 However, our results indicate that IL-33 is secreted from BM-resident P α S stromal cells under homeostatic conditions.”
Lack of ST2 aggravates glioma invasiveness, vascular abnormality, and immune suppression
Wicher, G., Roy, A., Vaccaro, A., Vemuri, K., Ramachandran, M., Olofsson, T., Imbria, R.-N., Belting, M., Nilsson, G. P., Dimberg, A., et al. (2025) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaf010 · Cited by 1
“20–22 Upon CNS injury or disease, IL-33 derived from glial cells facilitates the release of proinflammatory chemokines from both microglia and astrocytes, 21,22 leading to recruitment of eg, microglia/macrophages to the injury site.”
Kolomeets, N. S. (2024) · Psikhiatriya · doi:10.30629/2618-6667-2023-21-7-46-64 · Cited by 1
Baranova, N. S., Gris, M. S., Baranov, A. A., Spirin, N., Artyuhov, A., Шакирова, К. М., & Nasonov, E. (2023) · Bulletin of Russian State Medical University · doi:10.24075/brsmu.2023.032 · Cited by 3
Interleukin-33: Friend or Enemy in the Fight against Tumors?
Gorbacheva, A. M., & Mitkin, N. A. (2019) · Molecular Biology · doi:10.1134/s0026893319050066 · Cited by 5
Yamada, S., Shimizu, M., Kuroda, M., Inoue, N., Sugimoto, N., & Yachie, A. (2018) · Clinical and Experimental Nephrology · doi:10.1007/s10157-018-1675-y · Cited by 3
Hamzaoui, K., Sassi, F. H., Salhi, M., & Hamzaoui, A. (2025) · Immunology Letters · doi:10.1016/j.imlet.2025.107031 · Cited by 3
Chen, Z., Ford, K. P., Islam, M. B. A. R., Wan, H., Han, H., Ramakrishnan, A., Brown, R., Villanueva, V., Wang, Y., Davis, B. T., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03257-7 · Cited by 6
“This implies that the recruited monocytes are quickly converted to anti-inflammatory macrophages at the site of injury and participate in the repair process [47, 48].”
BackgroundST2 levels and neurodegenerative diseases: is this a significant relation?
Arora, H., Javed, B., Kutikuppala, L. V. S., Chaurasia, M., Khullar, K., Kannan, S., & Varshitha, G. (2024) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000001939 · Cited by 3
“ST2 is expressed predominantly by microglia and astrocytes [6] .”
BackgroundWang, W. T., Ye, C.-H., Deng, Z., Wang, J., Zhang, L., Bao, L., Xu, B., Zhu, H. H., Guo, Y., & Zhang, W. (2023) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v15.i5.917 · Cited by 3
Rozario, C., Martínez‐Sobrido, L., McSorley, H. J., & Chauché, C. (2021) · Viruses · doi:10.3390/v13122519 · Cited by 5
Toscano, E. C. D. B., Lessa, J. M. K., de Oliveira, G. N. D., Gonçalves, A. P. D. F., Vieira, É., Rachid, M., & Teixeira, A. (2020) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2020.107351 · Cited by 2
D’Antoni, M. L., Kallianpur, K. J., Premeaux, T. A., Corley, M. J., Fujita, T., Laws, E. I., Ogata-Arakaki, D., Chow, D. C., Khadka, V. S., Shikuma, C. M., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02789 · Cited by 2
Still, K. M., Batista, S. J., O’Brien, C. A., Oyesola, O. O., Früh, S. P., Webb, L. M., Smirnov, I., Kovacs, M. A., Cowan, M. N., Hayes, N. W., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/338400 · Cited by 1
Interlinking interleukin-33 (IL-33), neuroinflammation and neuropathic pain
Ferraz, C. R., Rasquel-Oliveira, F. S., Borghi, S. M., Franciosi, A., de Carvalho, T. T., Saraiva‐Santos, T., Artero, N. A., Casagrande, R., & Verri, W. A., Jr. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820589-1.00016-6 · Cited by 2
The Role of the IL‐33/ST2 Axis in Nervous System Development and Diseases
Luo, Z., & Yang, J. (2026) · Immunology and Cell Biology · doi:10.1111/imcb.70138 · Cited by 2
“IL-33 is released after central nervous system (CNS) injury and acts on astrocytes and microglia to induce chemokine production and monocyte recruitment [31].”
Macrophage Plasticity: Phenotypic and Functional Profiles Across Pathological Microenvironments
Falda, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27125333
Kaikarytė, K., Vilkevičiūtė, A., Balnytė, R., Ulozienė, I., & Liutkevičienė, R. (2026) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2026.107253 · Cited by 1
Hang, H., Yao, Y., Wang, L., Liu, C., Zhao, J., Xu, B., Zhao, H., & Wu, G. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1739324 · Cited by 1
“Subcortical regions contain large white-matter tracts and deeper structural hubs; injury in these areas may lead to continued release of damage-associated signals, supporting prolonged monocyte recruitment (37, 38).”
Assessing the inflammation in pediatric MOGAD: Significance of CSF HMGB1 and related biomarkers
Wang, X., Zhao, R., Fan, J., Liu, C., Li, Z., Yang, H., & Wang, W. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1534172 · Cited by 1
“IL-33 is widely expressed in the human body and can produce in fl ammatory factors, affect the permeability function of the BBB (31), and cause functional impairment of the CNS (32).”
Wang, P., Hu, J., Chen, C., Jiang, Z., Zhang, Y., Lin, K., Liao, L., & Wang, X. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111194 · Cited by 2
Fonta, N., Pagé, N., Klimek, B., Piccinno, M., Liberto, G. D., Lemeille, S., Kreutzfeldt, M., Kastner, A. L., Ertuna, Y. I., Vincenti, I., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.09.602661
“The primary sources of IL-33 in the CNS are astrocytes during development (Vainchtein et al., 2018) and oligodendrocytes in adulthood (Gadani et al., 2015).”
BackgroundResultInfluentialChen, Z., Ford, K. P., Islam, M. B. A. R., Wan, H., Han, H., Ramakrishnan, A., Brown, R. J., Villanueva, V., Wang, Y., Davis, B. T., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.17.596673
“This implies that the recruited monocytes are quickly converted to anti-inflammatory macrophages at the site of injury and participate in the repair process (45, 46).”
BackgroundWu, Q., Hu, X., Guo, Y., Zhao, M., Wang, M., Feng, L., & Wang, D. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e31745 · Cited by 1
“In the central nervous system, IL-33 is constitutively expressed in oligo-dendrocytes [23], while ST2 is mainly expressed in microglia and astrocytes [9].”
BackgroundAhmadzadeh, K., Dizaji, S. R., Balabandian, M., Ramawad, H. A., & Yousefifard, M. (2023) · Annals of Laboratory Medicine · doi:10.3343/alm.2023.43.6.585 · Cited by 1
Role of IL-33/ST2 Axis in Chronic Inflammatory Neurological Disorderss
Dimitrijević, J., Arsenijević, A., Milovanović, M., Stojanović, B., Arsenijević, D., Milovanović, J., & Arsenijević, N. (2021) · Serbian Journal of Experimental and Clinical Research · doi:10.2478/sjecr-2020-0038
“IL-33 expression is distributed throughout the white matter areas such as corpus callosum (CC), anterior forceps of the CC, anterior commissure, hippocampal fringe and stria terminalis (15, 21).”
BackgroundInfluentialUne nouvelle mission pour l’IL-33
Dalmas, É. (2018) · médecine/sciences · doi:10.1051/medsci/2018227 · Cited by 1
Obesity and Diabetes: Implications for Brain-Immunometabolism
Dyken, P. C. V., & Lacoste, B. (2020) · Frontiers Research Topics · doi:10.3389/978-2-88963-585-6 · Cited by 1
Microglia and immune signaling as architects of the brain
Kim, A., Solek, C. M., & Ruthazer, E. S. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1936860
Interleukin-33 and its receptor: multifaceted roles and emerging therapeutic potential
Serve, S., & Löhning, M. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-026-01345-8 · Cited by 2
Ma, Z., Lu, Z., Zhou, Z., Wang, T., Zhang, J., Ma, Y., Niu, R., Zhang, L., Deng, J., & Zhao, Y. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188254
“Primary studies of spinal contusion and crush injuries confirm that this early peak, occurring within 24 h, is vital for blunting the acute neuroinflammatory response [6,58].”
Nagasawa, T. (2026) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2026.101340
“…lineage that participates at synaptic boundaries also occupies an organ-level boundary, communicating with resident and infiltrating immune compartments during stroke, spinal-cord injury, and neurodegeneration (Gadani et al., 2015; Pomeshchik et al., 2015; Yang et al., 2017; Still et al., 2020).”
Metadata
- Authors
- Gadani, S. P., Walsh, J. T., Smirnov, I., Zheng, J., & Kipnis, J.
- Affiliations
- University of Virginia (US)
- University of Virginia Medical Center (US)
- Corresponding author
- Gadani, Sachin P.
- Kipnis, Jonathan
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 85
- Issue
- 4
- Pages
- 703-709
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC12064979
- OpenAlex
- W2033591334
- Cited by
- 359
- References
- 34
- Citations by year
- 2026: 20 · 2025: 33 · 2024: 28 · 2023: 35 · 2022: 35 · 2021: 46 · 2020: 39 · 2019: 32 · 2018: 37 · 2017: 24 · 2016: 18 · 2015: 11
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM007267)
- National Institute of Neurological Disorders and Stroke (NS061973, R01NS061973)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- IL-33, central nervous system injury, neuroinflammation, oligodendrocytes, astrocytes, microglia, monocyte recruitment, chemokines, myeloid cell infiltration, M2 macrophages, functional recovery, innate immune response
- MeSH terms
- Interleukin-33, Interleukin-1 Receptor-Like 1 Protein, CX3C Chemokine Receptor 1, Animals, Animals, Newborn, Cells, Cultured, Central Nervous System Diseases, Disease Models, Animal, Female, Gene Expression Regulation, Interleukins, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Neuroglia, Neurons, Retinal Ganglion Cells, Receptors, Interleukin, Ki-67 Antigen, Receptors, Chemokine, Recovery of Function, Green Fluorescent Proteins, Mice, In Vitro Techniques
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