Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction
Open accessAbstract
In autoimmune arthritis, traditionally classified as a T helper (Th) type 1 disease, the activation of T cells results in bone destruction mediated by osteoclasts, but how T cells enhance osteoclastogenesis despite the anti-osteoclastogenic effect of interferon (IFN)-γ remains to be elucidated. Here, we examine the effect of various Th cell subsets on osteoclastogenesis and identify Th17, a specialized inflammatory subset, as an osteoclastogenic Th cell subset that links T cell activation and bone resorption. The interleukin (IL)-23–IL-17 axis, rather than the IL-12–IFN-γ axis, is critical not only for the onset phase, but also for the bone destruction phase of autoimmune arthritis. Thus, Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation.
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In rheumatoid arthritis, stimulation of bone resorption by osteoclasts is exclusively mediated by Th17 cells, which produce IL-17 to stimulate RANKL expression.
“The authors found that, in the pathophysiology of rheumatoid arthritis, the stimulation of bone resorption by osteoclasts is exclusively mediated by Th17 cells, which produce IL-17 to stimulate RANKL expression [15,18,19].”
From Osteoporosis: Molecular Pathology, Diagnostics, and Therapeutics (2023) · cites this paper as [19]
The paper identifies Th17 as the exclusive osteoclastogenic subset among known CD4+ T-cell lineages (p. 2) and reports that Th17-derived IL-17 promotes osteoclastogenesis, potentially by inducing RANKL on supporting cells (p. 5). It does not say that Th17 cells exclusively mediate osteoclast-driven bone resorption in rheumatoid arthritis: the introduction (p. 2) also describes indirect effects mediated by inflammatory cytokines from synovial cells. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTh17 cells are an osteoclastogenic CD4+ T cell population defined by their capacity to produce IL-17.
“Th17 cells are an osteoclastogenic population of CD4 + T cells (45,46) defined by the capacity to produce IL-17 (47).”
From Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics (2016) · cites this paper as [45]
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Mosmann, T. R., Cherwinski, H. M., Bond, M. W., Giedlin, M. A., & Coffman, R. L. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.7.2348 · Cited by 7,438 · see citing works
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992 · see citing works
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670 · see citing works
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742 · see citing works
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265 · see citing works
Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087 · see citing works
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906 · see citing works
Self-citationTakayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701 · see citing works
Self-citationSakaguchi, S. (2005) · Nature Immunology · doi:10.1038/ni1178 · Cited by 2,669 · see citing works
Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M. T., & Martin, T. J. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0367 · Cited by 2,317 · see citing works
Kong, Y.-Y., Feige, U., Sarosi, I., Bolon, B., Tafuri, A., Morony, S., Capparelli, C., Li, J., Elliott, R., McCabe, S., et al. (1999) · Nature · doi:10.1038/46303 · Cited by 1,856 · see citing works
Genetic regulation of osteoclast development and function
Teitelbaum, S. L., & Ross, F. (2003) · Nature reviews genetics · doi:10.1038/nrg1122 · Cited by 1,733 · see citing works
Kotake, S., Udagawa, N., Takahashi, N., Matsuzaki, K., Itoh, K., Ishiyama, S., Saito, S., Inoue, K., Kamatani, N., Gillespie, M. T., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5703 · Cited by 1,696 · see citing works
Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation
Murphy, C. A., Langrish, C. L., Chen, Y., Blumenschein, W., McClanahan, T., Kastelein, R. A., Sedgwick, J. D., & Cua, D. J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030896 · Cited by 1,669 · see citing works
Self-citationEssential role of Stat6 in IL-4 signalling
Takeda, K., Tanaka, T., Shi, W., Matsumoto, M., Minami, M., Kashiwamura, S.-I., Nakanishi, K., Yoshida, N., Kishimoto, T., & Akira, S. (1996) · Nature · doi:10.1038/380627a0 · Cited by 1,557 · see citing works
Self-citationImmune Response in Mice that Lack the Interferon-γ Receptor
Huang, S., Hendriks, W. J. A. J., Althage, A., Hemmi, S., Bluethmann, H., Kamijo, R., Vilček, J., Zinkernagel, R. M., & Aguet, M. (1993) · Science · doi:10.1126/science.8456301 · Cited by 1,551 · see citing works
Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.002 · Cited by 1,422 · see citing works
T-Cell mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ.
Takayanagi, H., Ogasawara, K., Hida, S., Chiba, T., Murata, S., Sato, K., Takaoka, A., Yokochi, T., Oda, H., Tanaka, K., et al. (2000) · Nature · doi:10.1038/35046102 · Cited by 1,358 · see citing works
Self-citationSuppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice
Nakae, S., Nambu, A., Sudo, K., & Iwakura, Y. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.11.6173 · Cited by 1,272 · see citing works
Self-citationDenosumab in postmenopausal women with low bone mineral density.
McClung, M. R., Lewiecki, E. M., Cohen, S. B., Bolognese, M. A., Woodson, G. C., Moffett, A. H., Peacock, M., Miller, P. D., Lederman, S. N., Chesnut, C. H., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa044459 · Cited by 1,228 · see citing works
Nakae, S., Komiyama, Y., Nambu, A., Sudo, K., Iwase, M., Homma, I., Sekikawa, K., Asano, M., & Iwakura, Y. (2002) · Immunity · doi:10.1016/s1074-7613(02)00391-6 · Cited by 1,053 · see citing works
Self-citationAutoamplification of NFATc1 expression determines its essential role in bone homeostasis
Asagiri, M., Sato, K., Usami, T., Ochi, S., Nishina, H., Yoshida, H., Morita, I., Wagner, E. F., Mak, T. W., Serfling, E., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051150 · Cited by 849 · see citing works
Self-citationCostimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis
Koga, T., Inui, M., Inoue, K., Kim, S., Suematsu, A., Kobayashi, E., Iwata, T., Ohnishi, H., Matozaki, T., Kodama, T., et al. (2004) · Nature · doi:10.1038/nature02444 · Cited by 828 · see citing works
Self-citationRANK-L and RANK: T Cells, Bone Loss, and Mammalian Evolution
Theill, L. E., Boyle, W. J., & Penninger, J. M. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064753 · Cited by 817 · see citing works
TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis.
Pettit, A. R., Ji, H., von Stechow, D., Müller, R., Goldring, S. R., Choi, Y., Benoist, C., & Gravallese, E. M. (2001) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63016-7 · Cited by 807 · see citing works
OSTEOIMMUNOLOGY: Interplay Between the Immune System and Bone Metabolism
Walsh, M. C., Kim, N., Kadono, Y., Rho, J., Lee, S. Y., Lorenzo, J., & Choi, Y. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090646 · Cited by 724 · see citing works
Self-citationHofbauer, L. C., Lacey, D. L., Dunstan, C. R., Spelsberg, T. C., Riggs, B. L., & Khosla, S. (1999) · Bone · doi:10.1016/s8756-3282(99)00162-3 · Cited by 630 · see citing works
Anti-TNF-α therapies: the next generation
Palladino, M. A., Bahjat, F. R., Theodorakis, E. A., & Moldawer, L. L. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1175 · Cited by 579 · see citing works
Osteoclasts are essential for TNF-α–mediated joint destruction
Redlich, K., Hayer, S., Ricci, R., David, J., Tohidast-Akrad, M., Kollias, G. A., Steiner, G. E., Smolen, J. S., Wagner, E. F., & Schett, G. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15582 · Cited by 534 · see citing works
Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells
Dong, C. (2006) · Nature reviews. Immunology · doi:10.1038/nri1807 · Cited by 487 · see citing works
Osteoclasts are essential for TNF-α-mediated joint destruction.
Redlich, K., Hayer, S., Ricci, R., David, J.-P., Tohidast-Akrad, M., Kollias, G., Steiner, G., Smolen, J. S., Wagner, E. F., & Schett, G. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215582 · Cited by 474 · see citing works
Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice
Vermeire, K., Heremans, H., Vandeputte, M., Huang, S., Billiau, A., & Matthys, P. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.11.5507 · Cited by 458 · see citing works
Activated T Lymphocytes Support Osteoclast Formation in Vitro
Horwood, N. J., Kartsogiannis, V., Quinn, J. M. W., Romas, E., Martin, T. J., & Gillespie, M. T. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1623 · Cited by 416 · see citing works
Mechanistic insight into osteoclast differentiation in osteoimmunology
Takayanagi, H. (2005) · Journal of Molecular Medicine · doi:10.1007/s00109-004-0612-6 · Cited by 413 · see citing works
Self-citationUdagawa, N., Horwood, N. J., Elliott, J., Mackay, A., Owens, J., Okamura, H., Kurimoto, M., Chambers, T. J., Martin, T. J., & Gillespie, M. T. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.6.1005 · Cited by 378 · see citing works
High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors
Manoury, B., Chiocchia, G., Bessis, N., Abehsira-Amar, O., Batteux, F., Muller, S., Huang, S., Boissier, M., & Fournier, C. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.11.5501 · Cited by 355 · see citing works
αvβ3and macrophage colony‐stimulating factor: partners in osteoclast biology
Ross, F. P., & Teitelbaum, S. L. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00331.x · Cited by 303 · see citing works
Dolhain, R. J. E. M., van der Heiden, A. N., ter Haar, N. T., Breedveld, F. C., & Miltenburg, A. M. M. (1996) · Arthritis & Rheumatism · doi:10.1002/art.1780391204 · Cited by 295 · see citing works
Inflammatory bone destruction and osteoimmunology
Takayanagi, H. (2005) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2005.00814.x · Cited by 267 · see citing works
Self-citationIL-12 Alone and in Synergy with IL-18 Inhibits Osteoclast Formation In Vitro
Horwood, N. J., Elliott, J., Martin, T. J., & Gillespie, M. T. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.8.4915 · Cited by 248 · see citing works
RANK‐mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis
Gohda, J., Akiyama, T., Koga, T., Takayanagi, H., Tanaka, S., & Inoue, J. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600564 · Cited by 226 · see citing works
Self-citationOsteoclasts, rheumatoid arthritis, and osteoimmunology
Sato, K., & Takayanagi, H. (2006) · Current Opinion in Rheumatology · doi:10.1097/01.bor.0000231912.24740.a5 · Cited by 222 · see citing works
Self-citationKim, Y., Sato, K., Asagiri, M., Morita, I., Soma, K., & Takayanagi, H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505820200 · Cited by 198 · see citing works
Self-citationImmunohistochemical studies of interleukin‐2 and γ‐interferon in rheumatoid arthritis
Husby, G., & Williams, R. C. (1985) · Arthritis & Rheumatism · doi:10.1002/art.1780280212 · Cited by 96 · see citing works
Strength of TRAF6 signalling determines osteoclastogenesis
Kadono, Y., Okada, F., Perchonock, C. E., Jang, H. D., Lee, S. Y., Kim, N., & Choi, Y. (2005) · EMBO Reports · doi:10.1038/sj.embor.7400345 · Cited by 87 · see citing works
Self-citationHong, M. H., Williams, H., Jin, C., & Pike, J. W. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.5.911 · Cited by 76 · see citing works
Huang, W., O'Keefe, R., & Schwarz, E. (2002) · Arthritis Research & Therapy · doi:10.1186/ar612 · Cited by 69 · see citing works
The Role of T-lymphocytes and Cytokines in Rheumatoid Arthritis
Smolen, J. S., Tohidast-Akrad, M., Gal, A., et al. (1996) · Scandinavian Journal of Rheumatology · doi:10.3109/03009749609082660 · Cited by 64 · see citing works
T-cells in the pathogenesis of rheumatoid arthritis Villains or accomplices?
Kinne, R. W., Palombo‐Kinne, E., & Emmrich, F. (1997) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(96)00079-8 · Cited by 53 · see citing works
Effects of T cell adoptive transfer into nude mice on alveolar bone resorption induced by endotoxin
Ukai, T., Hara, Y., & Kato, L. (1996) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.1996.tb00510.x · Cited by 44 · see citing works
Hikita, A., Kadono, Y., Chikuda, H., Fukuda, A., Wakeyama, H., Yasuda, H., Nakamura, K., Oda, H., Miyazaki, T., & Tanaka, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507000200 · Cited by 31 · see citing works
Self-citationGravellese (2000) · Pure Amsterdam UMC · doi:10.1002/1529-0131(200002)43:2 · Cited by 2 · see citing works
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Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · see citing works
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873 · see citing works
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Sommer, F., & Bäckhed, F. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2974 · Cited by 3,681 · see citing works
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems
Takayanagi, H. (2007) · Nature Reviews Immunology · doi:10.1038/nri2062 · Cited by 1,878 · see citing works
Self-citationInterleukin-17 and Type 17 Helper T Cells
Miossec, P., Korn, T., & Kuchroo, V. K. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0707449 · Cited by 1,409 · see citing works
Functional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289 · see citing works
Self-citationPathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis
Komatsu, N., Okamoto, K., Sawa, S., Nakashima, T., Oh-hora, M., Kodama, T., Tanaka, S., Bluestone, J. A., & Takayanagi, H. (2014) · Nature Medicine · doi:10.1038/nm.3432 · Cited by 1,153 · see citing works
Self-citationBone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment
Schett, G., & Gravallese, E. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.153 · Cited by 947 · see citing works
Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease
Onishi, R. M., & Gaffen, S. L. (2010) · Immunology · doi:10.1111/j.1365-2567.2009.03240.x · Cited by 894 · see citing works
The gut microbiota regulates bone mass in mice
Sjögren, K., Engdahl, C., Henning, P., Lerner, U. H., Tremaroli, V., Lagerquist, M. K., Bäckhed, F., & Ohlsson, C. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1588 · Cited by 822 · see citing works
Interaction between bone and immune cells: Implications for postmenopausal osteoporosis
Fischer, V., & Haffner-Luntzer, M. (2022) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2021.05.014 · Cited by 759 · see citing works
Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics
Li, J.-Y., Chassaing, B., Tyagi, A. M., Vaccaro, C., Luo, T., Adams, J., Darby, T. M., Weitzmann, M. N., Mulle, J. G., Gewirtz, A. T., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86062 · Cited by 643 · see citing works
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He, F. J., Tan, M., Ma, Y., & MacGregor, G. A. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.055 · Cited by 589 · see citing works
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Kuwabara, T., Ishikawa, F., Kondo, M., & Kakiuchi, T. (2017) · Mediators of Inflammation · doi:10.1155/2017/3908061 · Cited by 519 · see citing works
RANK/RANKL: Regulators of Immune Responses and Bone Physiology
Leibbrandt, A., & Penninger, J. M. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.016 · Cited by 420 · see citing works
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Ono, T., Okamoto, K., Nakashima, T., Nitta, T., Hori, S., Iwakura, Y., & Takayanagi, H. (2016) · Nature Communications · doi:10.1038/ncomms10928 · Cited by 371 · see citing works
Self-citationGaffen, S. L., & Hajishengallis, G. (2008) · Journal of Dental Research · doi:10.1177/154405910808700908 · Cited by 334 · see citing works
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Briot, K., & Roux, C. (2015) · RMD Open · doi:10.1136/rmdopen-2014-000014 · Cited by 300 · see citing works
Effects of inflammatory and anti‐inflammatory cytokines on the bone
Schett, G. (2011) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2011.02545.x · Cited by 292 · see citing works
IL-17/Th17 targeting: On the road to prevent chronic destructive arthritis?
Lubberts, E. (2008) · Cytokine · doi:10.1016/j.cyto.2007.09.014 · Cited by 289 · see citing works
Inflammatory osteolysis: A conspiracy against bone
Mbalaviele, G., Novack, D. V., Schett, G., & Teitelbaum, S. L. (2017) · Journal of Clinical Investigation · doi:10.1172/jci93356 · Cited by 251 · see citing works
Fracture healing is accelerated in the absence of the adaptive immune system
Toben, D., Schroeder, I., El Khassawna, T., Mehta, M., Hoffmann, J.-E., Frisch, J.-T., Schell, H., Lienau, J., Serra, A., Radbruch, A., et al. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.185 · Cited by 236 · see citing works
Modulation of bone remodeling by the gut microbiota: A new therapy for osteoporosis
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Maitra, A., Shen, F., Hanel, W., Mossman, K., Tocker, J., Swart, D., & Gaffen, S. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611589104 · Cited by 165 · see citing works
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Vieira Ribeiro, F., de Mendonça, A. C., Santos, V. R., Bastos, M. F., Figueiredo, L. C., & Duarte, P. M. (2011) · Journal of Periodontology · doi:10.1902/jop.2011.100643 · Cited by 121 · see citing works
Zaiss, M. M., Sarter, K., Hess, A., Engelke, K., Böhm, C., Nimmerjahn, F., Voll, R., Schett, G., & David, J. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27535 · Cited by 122 · see citing works
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Cline-Smith, A., Axelbaum, A., Shashkova, E., Chakraborty, M., Sanford, J., Panesar, P., Peterson, M., Cox, L., Baldan, A., Veis, D., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3966 · Cited by 108 · see citing works
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Gallois, A., Lachuer, J., Yvert, G., Wierinckx, A., Brunet, F., Rabourdin-Combe, C., Delprat, C., Jurdic, P., & Mazzorana, M. (2010) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.090829 · Cited by 75 · see citing works
The inflammatory phase of fracture healing is influenced by oestrogen status in mice
Haffner-Luntzer, M., Fischer, V., Prystaz, K., Liedert, A., & Ignatius, A. (2017) · European Journal of Medical Research · doi:10.1186/s40001-017-0264-y · Cited by 60 · see citing works
Detection of IL-17 and IL-23 in Plasma Samples of Children with Autism
Enstrom, A., Onore, C., Hertz-Picc, I., Hansen, R., Croen, L., Water, J. V. D., & Ashwood, P. (2008) · American Journal of Biochemistry and Biotechnology · doi:10.3844/ajbbsp.2008.114.120 · Cited by 51 · see citing works
Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice
Dar, H. Y., Perrien, D. S., Pal, S., Stoica, A., Uppuganti, S., Nyman, J. S., Jones, R. M., Weitzmann, M. N., & Pacifici, R. (2023) · Journal of Clinical Investigation · doi:10.1172/jci166577 · Cited by 48 · see citing works
Sialylation of TLR2 initiates osteoclast fusion
Dou, C., Zhen, G., Dan, Y., Wan, M., Limjunyawong, N., & Cao, X. (2022) · Bone Research · doi:10.1038/s41413-022-00186-0 · Cited by 46 · see citing works
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Schmidt, T., Schwinge, D., Rolvien, T., Jeschke, A., Schmidt, C., Neven, M., Butscheidt, S., Kriz, M., Kunzmann, L., Mussawy, H., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.12.035 · Cited by 42 · see citing works
Ledesma-Colunga, M. G., Adán, N., Ortiz, G., Solís-Gutiérrez, M., López-Barrera, F., Martínez de la Escalera, G., & Clapp, C. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1290-4 · Cited by 40 · see citing works
Okamoto, K., & Takayanagi, H. (2023) · Bone · doi:10.1016/j.bone.2023.116675 · Cited by 42 · see citing works
Self-citationUpdate on the role of Interleukin 17 in rheumatologic autoimmune diseases
Konya, C., Paz, Z., Apostolidis, S. A., & Tsokos, G. C. (2015) · Cytokine · doi:10.1016/j.cyto.2015.01.003 · Cited by 35 · see citing works
Estrogen Deficiency, Postmenopausal Osteoporosis, and Age-Related Bone Loss
Khosla, S., & Pacifici, R. (2013) · Osteoporosis · doi:10.1016/b978-0-12-415853-5.00046-7 · Cited by 31 · see citing works
Schistosome infection promotes osteoclast-mediated bone loss
Li, W., Wei, C., Xu, L., Yu, B., Chen, Y., Lu, D., Zhang, L., Song, X., Dong, L., Zhou, S., et al. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009462 · Cited by 22 · see citing works
Zhang, W., Zhang, Y., Hu, N., & Wang, A. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.990779 · Cited by 12 · see citing works
Xie, D., Wang, Y., Li, J., Yang, T., Zhang, Y., Zhang, W., Doherty, M., Zhu, Y., Yang, Z., Wang, Y., et al. (2025) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2025.07.004 · Cited by 8 · see citing works
Osteoimmunology: The effect of autoimmunity on fracture healing and skeletal analysis
Lončar, S. R., Halcrow, S. E., & Swales, D. (2023) · Forensic Science International: Synergy · doi:10.1016/j.fsisyn.2023.100326 · Cited by 3 · see citing works
- Authors
- Sato, K., Suematsu, A., Okamoto, K., Yamaguchi, A., Morishita, Y., Kadono, Y., Tanaka, S., Kodama, T., Akira, S., Iwakura, Y., Cua, D. J., & Takayanagi, H.
- Affiliations
- Tokyo Medical and Dental University (JP)
- 2Department of Oral Pathology, Graduate School, and
- 4Department of Human Pathology and
- The University of Tokyo (JP)
- Research Center for Advanced Science and Technology, The University of Tokyo (JP)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- 9Discovery Research, DNAX Research Inc., Palo Alto, CA 94304
- ORCID
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-11-06
- Volume
- 203
- Issue
- 12
- Pages
- 2673-2682
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2118166
- OpenAlex
- W2114982159
- Cited by
- 1,554
- References
- 52
- Citations by year
- 2026: 56 · 2025: 58 · 2024: 78 · 2023: 82 · 2022: 68 · 2021: 78 · 2020: 90 · 2019: 77 · 2018: 82 · 2017: 73 · 2016: 70 · 2015: 91 · 2014: 89 · 2013: 85 · 2012: 97
- FWCI
- 29.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- Th17 cells, osteoclastogenesis, bone destruction, autoimmune arthritis, IL-23, IL-17, interferon-gamma, T cell activation, bone resorption, therapeutic target
- MeSH terms
- Animals, Arthritis, Experimental, Bone and Bones, Bone Resorption, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Lymphocyte Activation, Mice, Inbred C57BL, Osteoclasts, T-Lymphocyte Subsets, Mice, Knockout, Mice
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