IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo
Open accessAbstract
Recent studies indicate that IL-1α functions intracellularly in pathways independent of its cell surface receptors by translocating to the nucleus and regulating transcription. Similarly, the chromatin-associated protein HMGB1 acts as both a nuclear factor and a secreted proinflammatory cytokine. Here, we show that IL-33, an IL-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines, is an endothelium-derived, chromatin-associated nuclear factor with transcriptional repressor properties. We found that IL-33 is identical to NF-HEV, a nuclear factor preferentially expressed in high endothelial venules (HEV), that we previously characterized. Accordingly, in situ hybridization demonstrated that endothelial cells constitute a major source of IL-33 mRNA in chronically inflamed tissues from patients with rheumatoid arthritis and Crohn's disease. Immunostaining with three distinct antisera, directed against the N-terminal part and IL-1-like C-terminal domain, revealed that IL-33 is a heterochromatin-associated nuclear factor in HEV endothelial cells in vivo . Association of IL-33 with heterochromatin was also observed in human and mouse cells under living conditions. In addition, colocalization of IL-33 with mitotic chromatin was noted. Nuclear localization, heterochromatin-association, and targeting to mitotic chromosomes were all found to be mediated by an evolutionarily conserved homeodomain-like helix–turn–helix motif within the IL-33 N-terminal part. Finally, IL-33 was found to possess transcriptional repressor properties, associated with the homeodomain-like helix–turn–helix motif. Together, these data suggest that, similarly to IL1α and HMGB1, IL-33 is a dual function protein that may function as both a proinflammatory cytokine and an intracellular nuclear factor with transcriptional regulatory properties.
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IL-33 is highly expressed within endothelial cells in the synovium of patients with rheumatoid arthritis.
“IL-33 is highly expressed within endothelial cells in the synovium of patients with rheumatoid arthritis87, and IL-33-deficient mice have reduced neutrophil migration in an experimental model of rheumatoid arthritis88, but the actual role of this cytokine in the pathogenesis of rheumatoid arthritis or other sterile inflammatory diseases remains to be determined.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [87]
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Cites
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221 · see citing works
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 3,701 · see citing works
HMG-1 as a Late Mediator of Endotoxin Lethality in Mice
Wang, H., Bloom, O., Zhang, M., Vishnubhakat, J. M., Ombrellino, M., Che, J., Frazier, A., Yang, H., Ivanova, S., Borovikova, L. V., et al. (1999) · Science · doi:10.1126/science.285.5425.248 · Cited by 3,386 · see citing works
Biologic basis for interleukin-1 in disease.
Dinarello, C. (1996) · Blood · doi:10.1182/blood.v87.6.2095.bloodjournal8762095 · Cited by 3,380 · see citing works
Yang, Y., Li, S., Yang, Q., Shi, Y., Zheng, M., Liu, Y., Chen, F., Song, G., Xu, H., Wan, T., et al. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000358696 · Cited by 3,262 · see citing works
High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal
Lotze, M. T., & Tracey, K. J. (2005) · Nature reviews. Immunology · doi:10.1038/nri1594 · Cited by 2,490 · see citing works
Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
Bonaldi, T., Talamo, F., Scaffidi, P., Ferrera, D., Porto, A., Bachi, A., Rubartelli, A., Agresti, A., & Bianchi, M. E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg516 · Cited by 1,252 · see citing works
Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin.
Brown, K., Guest, S. S., Smale, S., Hahm, K., Merkenschlager, M., & Fisher, A. (1997) · Cell · doi:10.1016/s0092-8674(00)80472-9 · Cited by 824 · see citing works
HMG1 and 2, and related ‘architectural’ DNA-binding proteins
Thomas, J. O., & TRAVERS, A. A. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01801-1 · Cited by 619 · see citing works
Ikaros DNA-Binding Proteins Direct Formation of Chromatin Remodeling Complexes in Lymphocytes
Kim, J., Sif, S., Jones, B., Jackson, A., Koipally, J., Heller, E., Winandy, S., Viel, A., Sawyer, A., Ikeda, T., et al. (1999) · Immunity · doi:10.1016/s1074-7613(00)80034-5 · Cited by 587 · see citing works
Townsend, M. J., Fallon, P. G., Matthews, D. J., Jolin, H. E., & McKenzie, A. N. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.6.1069 · Cited by 482 · see citing works
Bækkevold, E. S., Roussigné, M., Yamanaka, T., Johansen, F., Jahnsen, F. L., Amalric, F., Brandtzæg, P., Érard, M., Haraldsen, G., & Girard, J. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63631-0 · Cited by 474 · see citing works
Self-citationExtension of the Life-Span of Human Endothelial Cells by an Interleukin-1αAntisense Oligomer
Maier, J. A. M., Voulalas, P. J., Roeder, D., & Maciag, T. (1990) · Science · doi:10.1126/science.2218499 · Cited by 397 · see citing works
HMGB proteins and gene expression
Agresti, A., & Bianchi, M. E. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(03)00023-6 · Cited by 394 · see citing works
Coyle, A. J., Lloyd, C. M., Tian, J. Y., Nguyen, T. T. T., Erikkson, C., Wang, L., Ottoson, P., Persson, P. O., Delaney, T. A., Lehar, S. M., et al. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.7.895 · Cited by 370 · see citing works
The precursor form of IL-1α is an intracrine proinflammatory activator of transcription
Werman, A., Werman-Venkert, R., White, R. M., Lee, J.-K., Werman, B., Krelin, Y., Voronov, E., Dinarello, C. A., & Apte, R. N. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308705101 · Cited by 346 · see citing works
Haematopoietic cell-fate decisions, chromatin regulation and ikaros
Georgopoulos, K. (2002) · Nature reviews. Immunology · doi:10.1038/nri747 · Cited by 324 · see citing works
Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes
Koipally, J., Renold, A., Kim, J., & Georgopoulos, K. (1999) · The EMBO Journal · doi:10.1093/emboj/18.11.3090 · Cited by 304 · see citing works
Zhang, J. D., Cousens, L. S., Barr, P. J., & Sprang, S. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.8.3446 · Cited by 250 · see citing works
Annotating genes with potential roles in the immune system: six new members of the IL-1 family
Dunn, E., Sims, J. E., Nicklin, M. J. H., & O'Neill, L. A. J. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(01)02034-8 · Cited by 234 · see citing works
Interleukin-18, a proinflammatory cytokine.
Dinarello, C. A. (2000) · PubMed · Cited by 233 · see citing works
Vandel, L., Nicolas, E., Vaute, O., Ferreira, R., Ait‐Si‐Ali, S., & Trouche, D. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.19.6484-6494.2001 · Cited by 214 · see citing works
Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism
Kaplanski, G., Farnarier, C., Kaplanski, S., Porat, R., Shapiro, L., Bongrand, P., & Dinarello, C. A. (1994) · Blood · doi:10.1182/blood.v84.12.4242.bloodjournal84124242 · Cited by 209 · see citing works
Lacorre, D.-A., Bækkevold, E. S., Garrido, I., Brandtzæg, P., Haraldsen, G., Amalric, F., & Girard, J. (2004) · Blood · doi:10.1182/blood-2003-10-3537 · Cited by 189 · see citing works
Self-citationMembrane interleukin 1 induction on human endothelial cells and dermal fibroblasts.
Kurt‐Jones, E. A., Fiers, W. C., & Pober, J. S. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.139.7.2317 · Cited by 168 · see citing works
Wessendorf, J., Garfinkel, S., Zhan, X., Brown, S., & Maciag, T. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80653-x · Cited by 154 · see citing works
Crystal structure of the cytokine interleukin‐1 beta.
Priestle, J. P., Schär, H., & Grütter, M. G. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb02818.x · Cited by 152 · see citing works
Pallier, C., Scaffidi, P., Chopineau-Proust, S., Agresti, A., Nordmann, P., Bianchi, M. E., & Maréchal, V. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-09-0581 · Cited by 137 · see citing works
Maier, J. A. M., Statuto, M., & Ragnotti, G. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1845 · Cited by 131 · see citing works
An IL-1 Family Member Requires Caspase-1 Processing and Signals through the ST2 Receptor
Dinarello, C. A. (2005) · Immunity · doi:10.1016/j.immuni.2005.10.004 · Cited by 131 · see citing works
Middleton, J., Americh, L., Gayon, R., Julien, D., Mansat, M., Mansat, P., Anract, P., Cantagrel, A. G., Cattan, P., Reimund, J., et al. (2005) · The Journal of Pathology · doi:10.1002/path.1788 · Cited by 119 · see citing works
Self-citationThe N-terminal propiece of interleukin 1α is a transforming nuclear oncoprotein
Stevenson, F. T., Turck, J., Locksley, R. M., & Lovett, D. H. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.2.508 · Cited by 113 · see citing works
Intracellular Interleukin-1α Functionally Interacts with Histone Acetyltransferase Complexes
Buryskova, M., Pospíšek, M., Grothey, A., Simmet, T., & Burýšek, L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306342200 · Cited by 98 · see citing works
Unconventional Potentiation of Gene Expression by Ikaros
Koipally, J., Heller, E. J., Seavitt, J. R., & Georgopoulos, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111371200 · Cited by 80 · see citing works
Hu, B., Wang, S., Zhang, Y., Feghali, C. A., Dingman, J. R., & Wright, T. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1737765100 · Cited by 75 · see citing works
Maier, J. A. M., Statuto, M., & Ragnotti, G. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1845-1851.1994 · Cited by 46 · see citing works
Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium
Patterson, A. M., Gardner, L., Shaw, J., David, G., Loreau, E., Aguilar, L., Ashton, B. A., & Middleton, J. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21222 · Cited by 44 · see citing works
Self-citationMcMahon, G. A., Garfinkel, S., Prudovsky, I. A., Hu, X., & Maciag, T. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28202 · Cited by 44 · see citing works
Palmeri, D., Zuo, F., Rosen, S. D., & Hemmerich, S. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0903408 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [1]Dinarello CA. Blood. 1996;87:2095–2147. [PubMed] [Google Scholar]
- [2]Dinarello CA. Eur Cytokine Netw. 2000;11:483–486. [PubMed] [Google Scholar]
- [10]Kaplanski G, Farnarier C, Kaplanski S, Porat R, Shapiro L, Bongrand P, Dinarello CA. Blood. 1994;84:4242–4248. [PubMed] [Google Scholar]
- [17]Wessendorf JH, Garfinkel S, Zhan X, Brown S, Maciag T. J Biol Chem. 1993;268:22100–22104. [PubMed] [Google Scholar]
- [25]Kurt-Jones EA, Fiers W, Pober JS. J Immunol. 1987;139:2317–2324. [PubMed] [Google Scholar]
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Immunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466 · see citing works
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Bonilla, W. V., Fröhlich, A., Senn, K., Kallert, S. M., Fernandez, M., Johnson, S., Kreutzfeldt, M., Hegazy, A. N., Schrick, C., Fallon, P. G., et al. (2012) · Science · doi:10.1126/science.1215418 · Cited by 417 · see citing works
IL-33, a Potent Inducer of Adaptive Immunity to Intestinal Nematodes
Humphreys, N. E., Xu, D., Hepworth, M. R., Liew, F. Y., & Grencis, R. K. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2443 · Cited by 417 · see citing works
Pastorelli, L., Garg, R. R., Hoang, S. B., Spina, L., Mattioli, B., Scarpa, M., Fiocchi, C., Vecchi, M. L., & Pizarro, T. T. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912678107 · Cited by 418 · see citing works
Li, D., Guabiraba, R., Besnard, A., Komai‐Koma, M., Jabir, M. S., Zhang, L., Graham, G. J., Kurowska‐Stolarska, M., Liew, F. Y., McSharry, C. P., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.05.011 · Cited by 414 · see citing works
Interleukin 33 is a guardian of barriers and a local alarmin
Martin, N., & Martin, M. (2016) · Nature Immunology · doi:10.1038/ni.3370 · Cited by 393 · see citing works
Lefrançais, E., Duval, A., Mirey, E., Roga, S., Espinosa, É., Cayrol, C., & Girard, J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410700111 · Cited by 385 · see citing works
Self-citationBarlow, J. L., Peel, S. E., Fox, J., Panova, V., Hardman, C. S., Camelo, A., Bucks, C. M., Wu, X., Kane, C. M., Neill, D. R., et al. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.05.012 · Cited by 383 · see citing works
Baliwag, J., Barnes, D. H., & Johnston, A. (2015) · Cytokine · doi:10.1016/j.cyto.2014.12.014 · Cited by 382 · see citing works
The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders
Barksby, H. E., Lea, S., Preshaw, P. M., & Taylor, J. J. (2007) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2007.03441.x · Cited by 372 · see citing works
The IL-1 family of cytokines and receptors in rheumatic diseases
Dinarello, C. A. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0277-8 · Cited by 368 · see citing works
Peiser, M., Tralau, T., Heidler, J., Api, A. M., Arts, J. H. E., Basketter, D. A., English, J. S. C., Diepgen, T. L., Fuhlbrigge, R. C., Gaspari, A. A., et al. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0846-8 · Cited by 361 · see citing works
Inflammasomes: current understanding and open questions
Bauernfeind, F. G., Ablasser, A., Bartok, E., Kim-Hellmuth, S., Schmid-Burgk, J. L., Cavlar, T., & Hornung, V. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0567-4 · Cited by 356 · see citing works
Dealing with danger in the CNS: the response of the immune system to injury
Gadani, S. P., Walsh, J. T., Lukens, J. R., & Kipnis, J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.019 · Cited by 342 · see citing works
Cells of the synovium in rheumatoid arthritis
Kinne, M., Stuhlmüller, B., & Burmester, G.-R. (2007) · Cited by 334 · see citing works
IL‐33‐activated dendritic cells are critical for allergic airway inflammation
Besnard, A., Togbe, D., Guillou, N., Erard, F., Quesniaux, V. F. J., & Ryffel, B. (2011) · European Journal of Immunology · doi:10.1002/eji.201041033 · Cited by 331 · see citing works
Bourgeois, E. A., Pham, L., Samson, M., Diem, S., Barra, A., Roga, S., Gombert, J., Schneider, E., Dy, M., Gourdy, P., et al. (2009) · European Journal of Immunology · doi:10.1002/eji.200838575 · Cited by 329 · see citing works
Self-citationBoezen, H. M. (2009) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200907-058dp · Cited by 341 · see citing works
Cayrol, C., & Girard, J. (2022) · Cytokine · doi:10.1016/j.cyto.2022.155891 · Cited by 335 · see citing works
Self-citationAli, S., Huber, M., Kollewe, C., Bischoff, S. C., Falk, W., & Martin, M. U. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705939104 · Cited by 325 · see citing works
Ali, S., Mohs, A., Thomas, M., Klare, J., Ross, R., Schmitz, M. L., & Martin, M. U. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003080 · Cited by 324 · see citing works
Johnston, A., Xing, X., Guzman, A. M., Riblett, M., Loyd, C. M., Ward, N. L., Wohn, C., Prens, E. P., Wang, F., Maier, L. E., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003162 · Cited by 319 · see citing works
An IL-1 Cytokine Member, IL-33, Induces Human Basophil Activation via Its ST2 Receptor
Suzukawa, M., Iikura, M., Koketsu, R., Nagase, H., Tamura, C., Komiya, A., Nakae, S., Matsushima, K., Ohta, K., Yamamoto, K., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.5981 · Cited by 316 · see citing works
Kim, H. Y., Chang, Y., Subramanian, S., Lee, H.-H., Albacker, L. A., Matangkasombut, P., Savage, P. B., McKenzie, A. N. J., Smith, D. E., Rottman, J. B., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.10.036 · Cited by 316 · see citing works
Inhibition of interleukin‐33 signaling attenuates the severity of experimental arthritis
Palmer, G., Talabot‐Ayer, D., Lamacchia, C., Toy, D. Y., Seemayer, C. A., Viatte, S., Finckh, A., Smith, D. E., & Gabay, C. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24305 · Cited by 313 · see citing works
Primer: inflammasomes and interleukin 1β in inflammatory disorders
Church, L. D., Cook, G. P., & McDermott, M. (2008) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0681 · Cited by 312 · see citing works
Current trends in inflammatory and immunomodulatory mediators in sepsis
Aziz, M., Jacob, A., Yang, W.-L., Matsuda, A., & Wang, P. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0912437 · Cited by 309 · see citing works
Interleukin-33 – cytokine of dual function or novel alarmin?
Haraldsen, G., Balogh, J., Pollheimer, J., Sponheim, J., & Küchler, A. M. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.03.003 · Cited by 309 · see citing works
Jiang, H., Milovanović, M., Allan, D., Niedbała, W., Besnard, A., Fukada, S. Y., Alves-Filho, J. C., Togbe, D., Goodyear, C. S., Linington, C., et al. (2012) · European Journal of Immunology · doi:10.1002/eji.201141947 · Cited by 307 · see citing works
Cells of the synovium in rheumatoid arthritis. Macrophages
Kinne, R. W., Stuhlmüller, B., & Burmester, G. R. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2333 · Cited by 526 · see citing works
Roussel, L., Érard, M., Cayrol, C., & Girard, J. (2008) · EMBO Reports · doi:10.1038/embor.2008.145 · Cited by 300 · see citing works
Self-citationNew fronts emerge in the influenza cytokine storm
Guo, X.-Z. J., & Thomas, P. G. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0636-y · Cited by 295 · see citing works
The IL-1 cytokine family and its role in inflammation and fibrosis in the lung
Borthwick, L. A. (2016) · Seminars in Immunopathology · doi:10.1007/s00281-016-0559-z · Cited by 294 · see citing works
Interleukin 33 as a Mechanically Responsive Cytokine Secreted by Living Cells
Kakkar, R. K., Hei, H., Dobner, S., & Lee, R. T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.298703 · Cited by 297 · see citing works
IL-33 Exacerbates Eosinophil-Mediated Airway Inflammation
Stolarski, B., Kurowska‐Stolarska, M., Kewin, P., Xu, D., & Liew, F. Y. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000730 · Cited by 291 · see citing works
Suppression of inflammation and acquired immunity by IL ‐37
Cavalli, G., & Dinarello, C. A. (2017) · Immunological Reviews · doi:10.1111/imr.12605 · Cited by 291 · see citing works
IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcεRI signals
Ho, L. H., Ohno, T., Oboki, K., Kajiwara, N., Suto, H., Iikura, M., Okayama, Y., Akira, S., Saito, H., Galli, S. J., et al. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0407200 · Cited by 285 · see citing works
IL33: Roles in Allergic Inflammation and Therapeutic Perspectives
Chan, B. C.-L., Lam, C. W. K., Tam, L., & Wong, C. K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00364 · Cited by 285 · see citing works
IL-1 Family Cytokine Regulation of Vascular Permeability and Angiogenesis
Fahey, E., & Doyle, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01426 · Cited by 276 · see citing works
Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation
Hong, H., Liao, S., Chen, F., Yang, Q., & Wang, D. Y. (2020) · Allergy · doi:10.1111/all.14526 · Cited by 274 · see citing works
The role of the nucleosome acidic patch in modulating higher order chromatin structure
Kalashnikova, A. A., Porter-Goff, M. E., Muthurajan, U. M., Luger, K., & Hansen, J. C. (2013) · Journal of The Royal Society Interface · doi:10.1098/rsif.2012.1022 · Cited by 271 · see citing works
The role of cytokines in inflammatory bone loss
de Souza, P. C., & Lerner, U. H. (2013) · Immunological Investigations · doi:10.3109/08820139.2013.822766 · Cited by 272 · see citing works
IL‐1: Discoveries, controversies and future directions
Dinarello, C. A. (2010) · European Journal of Immunology · doi:10.1002/eji.201040319 · Cited by 270 · see citing works
Regulation of Mast Cell Responses in Health and Disease
Gilfillan, A. M., & Beaven, M. A. (2011) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v31.i6.30 · Cited by 258 · see citing works
IL-33/ST2 axis in inflammation and immunopathology
Milovanović, M., Volarević, V., Radosavljevic, G. D., Jovanović, I., Pejnovic, N. N., Arsenijević, N., & Lukić, M. L. (2012) · Immunologic Research · doi:10.1007/s12026-012-8283-9 · Cited by 256 · see citing works
Interleukin-33 overexpression is associated with liver fibrosis in mice and humans
Marvie, P., Lisbonne, M., L’Helgoualc’h, A., Rauch, M., Turlin, B., Preisser, L., Bourd‐Boittin, K., Théret, N., Gascan, H., Piquet‐Pellorce, C., et al. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00801.x · Cited by 251 · see citing works
IL ‐33: biological properties, functions, and roles in airway disease
Drake, L. Y., & Kita, H. (2017) · Immunological Reviews · doi:10.1111/imr.12552 · Cited by 251 · see citing works
Interleukin-33 Is Biologically Active Independently of Caspase-1 Cleavage
Talabot‐Ayer, D., Lamacchia, C., Gabay, C., & Palmer, G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m901744200 · Cited by 251 · see citing works
Bartúnek, J., Delrue, L., Durme, F. V., Müller, O., Casselman, F. P. A., Wiest, B. D., Croes, R., Verstreken, S., Goethals, M. A., RAEDT, H. D., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.09.027 · Cited by 244 · see citing works
Fibro–Adipogenic Progenitors Cross-Talk in Skeletal Muscle: The Social Network
Biferali, B., Proietti, D., Mozzetta, C., & Madaro, L. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01074 · Cited by 244 · see citing works
The IL-1 Family Member 7b Translocates to the Nucleus and Down-Regulates Proinflammatory Cytokines
Sharma, S., Kulk, N., Nold, M. F., Gräf, R., Kim, S., Reinhardt, D., Dinarello, C. A., & Bufler, P. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.8.5477 · Cited by 242 · see citing works
Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease
Beltrán, C. J., Núñez, L. E., Díaz-Jiménez, D., Farfán, N., Candía, E., Heine, C., López, F., González, M. J., Quera, R., & Hermoso, M. A. (2009) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21175 · Cited by 239 · see citing works
IL-33 Mediates Inflammatory Responses in Human Lung Tissue Cells
Yagami, A., Orihara, K., Morita, H., Futamura, K., Hashimoto, N., Matsumoto, K., Saito, H., & Matsuda, A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903818 · Cited by 237 · see citing works
- Authors
- Carriere, V., Roussel, L., Ortega, N., Lacorre, D.-A., Americh, L., Aguilar, L., Bouche, G., & Girard, J.-P.
- Affiliations
- *Laboratoire de Biologie Vasculaire, Equipe Labellisée “La Ligue 2006,” Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5089, 205 Route de Narbonne, 31077 Toulouse, France; and
- Centre National de la Recherche Scientifique (FR)
- Endocube, Prologue Biotech, BP700, Rue Pierre et Marie Curie, 31319 Labège Cedex, France
- Corresponding author
- Girard, Jean-Philippe
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-01-02
- Volume
- 104
- Issue
- 1
- Pages
- 282-287
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1765450
- OpenAlex
- W2093396768
- Cited by
- 966
- References
- 38
- Citations by year
- 2026: 20 · 2025: 29 · 2024: 30 · 2023: 49 · 2022: 50 · 2021: 51 · 2020: 47 · 2019: 51 · 2018: 58 · 2017: 55 · 2016: 64 · 2015: 70 · 2014: 52 · 2013: 56 · 2012: 72
- FWCI
- 12.14
- 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
- Association pour la Recherche sur le Cancer
- Drug Applied Research Center, Tabriz University of Medical Sciences
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- IL-33, ST2 receptor, heterochromatin, nuclear factors, transcriptional repressor, endothelial cells, high endothelial venules, rheumatoid arthritis, Crohn's disease, chronic inflammation, HMGB1
- MeSH terms
- Interleukin-33, Interleukin-1 Receptor-Like 1 Protein, Animals, Arthritis, Rheumatoid, Crohn Disease, HeLa Cells, Heterochromatin, Humans, Interleukins, Membrane Proteins, Mitosis, Nuclear Proteins, Receptors, Cell Surface, Repressor Proteins, RNA, Messenger, 3T3 Cells, Conserved Sequence, Receptors, Interleukin, Nuclear Localization Signals, Amino Acid Motifs, Endothelial Cells, Mice
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