IL-6-STAT3 Controls Intracellular MHC Class II αβ Dimer Level through Cathepsin S Activity in Dendritic Cells
Open accessAbstract
We found IL-6-STAT3 pathway suppresses MHC class II (MHCII) expression on dendritic cells (DCs) and attenuates T cell activation. Here, we showed that IL-6-STAT3 signaling reduced intracellular MHCII alphabeta dimmer, Ii, and H2-DM levels in DCs. IL-6-mediated STAT3 activation decreased cystatin C level, an endogenous inhibitor of cathepsins, and enhanced cathepsin activities. Importantly, cathepsin S inhibitors blocked reduction of MHCII alphabeta dimer, Ii, and H2-DM in the IL-6-treated DCs. Overexpression of cystatin C suppressed IL-6-STAT3-mediated increase of cathepsin S activity and reduction of MHCII alphabeta dimer, Ii, and H2-DM levels in DCs. Cathepsin S overexpression in DCs decreased intracellular MHCII alphabeta dimer, Ii, and H2-DM levels, LPS-mediated surface expression of MHCII and suppressed CD4(+) T cell activation. IL-6-gp130-STAT3 signaling in vivo decreased cystatin C expression and MHCII alphabeta dimer level in DCs. Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces the MHCII alphabeta dimer, Ii, and H2-DM levels in DCs, and suppresses CD4(+) T cell-mediated immune responses.
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CyC is a known potent inhibitor of cysteine proteases, such as those involved in antigen presentation.
“CyC is a known potent inhibitor of cysteine proteases,74 such as those involved in antigen presentation,75”
From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [75]
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- Drakesmith, H., O'Neil, D., Schneider, S.C., Binks, M., Medd, P., Sercarz, E., Beverley, P., and Chain, B. (1998). In vivo priming of T cells against cryptic determinants by dendritic cells exposed to interleukin 6 and native antigen. Proc. Natl. Acad. Sci. USA 95 , 14903-14908.
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Liu, T., Han, C., Wang, S., Fang, P., Ma, Z., Xu, L., & Yin, R. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0770-1 · Cited by 860 · see citing works
Hillmer, E. J., Zhang, H., Li, H. S., & Watowich, S. S. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.05.001 · Cited by 740 · see citing works
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Self-citationvan de Laar, L., Coffer, P. J., & Woltman, A. M. (2012) · Blood · doi:10.1182/blood-2011-11-370130 · Cited by 362 · see citing works
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Wölfle, S. J., Strebovsky, J., Bartz, H., Sähr, A., Arnold, C., Kaiser, C., Dalpke, A. H., & Heeg, K. M. (2010) · European Journal of Immunology · doi:10.1002/eji.201040979 · Cited by 325 · see citing works
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Ziani, L., Chouaı̈b, S., & Thiery, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00414 · Cited by 379 · see citing works
Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
“(TLR)–induced proinflammatory mediators (Park et al., 2004; Kitamura et al., 2005; Cheng et al., 2008; Melillo et al., 2010; Wölfle et al., 2011); and 5) increased tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase and resultant T cell apoptosis mediated by kynurenine, a tryptophan…”
BackgroundKitamura, H., Ohno, Y., Toyoshima, Y., Ohtake, J., Homma, S., Kawamura, H., Takahashi, N., & Taketomi, A. (2017) · Cancer Science · doi:10.1111/cas.13332 · Cited by 278 · see citing works
Self-citationKrempski, J. W., Karyampudi, L., Behrens, M. D., Erskine, C. L., Hartmann, L. C., Dong, H., Goode, E. L., Kalli, K. R., & Knutson, K. L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100274 · Cited by 255 · see citing works
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Melillo, J. A., Song, L., Bhagat, G., Blazquez, A. B., Plumlee, C. R., Lee, C., Berin, C., Reizis, B., & Schindler, C. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902960 · Cited by 225 · see citing works
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Liang, S., Ristich, V., Arase, H., Dausset, J., Carosella, E., & Horuzsko, A. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0803341105 · Cited by 209
Cystatin C: current position and future prospects
Séronie-Vivien, S., Delanaye, P., Piéroni, L., Mariat, C., Froissart, M., & Cristol, J. (2008) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2008.336 · Cited by 204 · see citing works
CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion
Günaydın, G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.668349 · Cited by 205 · see citing works
Cysteine protease cathepsins in cardiovascular disease: from basic research to clinical trials
Liu, C.-L., Guo, J., Zhang, X., Sukhova, G. K., Libby, P., & Shi, G. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0002-3 · Cited by 212 · see citing works
Involvement of cystatin C in immunity and apoptosis
Zi, M., & Xu, Y. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.01.006 · Cited by 170 · see citing works
“In supporting this possibility, experiments using bone marrow-derived DCs indicated that interleukin (IL)-6 mediated signal transducer and activator of transcription 3 (STAT3) activation decreased cystatin C expression [36] .”
BackgroundInfluentialMolecular Control of Steady-State Dendritic Cell Maturation and Immune Homeostasis
Hammer, G. E., & Ma, A. I. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074929 · Cited by 156 · see citing works
Immune‐suppressive effects of interleukin‐6 on T‐cell‐mediated anti‐tumor immunity
Tsukamoto, H., Fujieda, K., Senju, S., Ikeda, T., Oshiumi, H., & Nishimura, Y. (2017) · Cancer Science · doi:10.1111/cas.13433 · Cited by 165 · see citing works
Urinary Biomarkers and Renal Recovery in Critically Ill Patients with Renal Support
Srisawat, N., Wen, X., Lee, M. J., Kong, L., Elder, M. M., Carter, M., Unruh, M. L., Finkel, K. W., Vijayan, A., Ramkumar, M., et al. (2011) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.11261210 · Cited by 165 · see citing works
Diverse regulatory roles for lysosomal proteases in the immune response
Colbert, J. D., Matthews, S. P., Miller, G., & Watts, C. (2009) · European Journal of Immunology · doi:10.1002/eji.200939650 · Cited by 131 · see citing works
Cancer-associated fibroblasts: The chief architect in the tumor microenvironment
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“Moreover, CAFs are known to regress the impact of cancer immunotherapy and favor tumor progression via the reduction of TH1 cells through their conversion into TH2 cells and generation of TH17 cells, respectively (Dikov et al., 2005; Kitamura et al., 2005; Flavell et al., 2010; Allard et al., 2016; Hashimoto et al., 2…”
BackgroundSTAT3, a master regulator of anti-tumor immune response
Rébé, C., & Ghiringhelli, F. (2019) · Cancers · doi:10.3390/cancers11091280 · Cited by 129 · see citing works
The role of cystatins in cells of the immune system
Kopitar-Jerala, N. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.10.055 · Cited by 129 · see citing works
“showed that interleukin-6 (IL-6)-mediated signalling increased cathepsin S activity, significantly reduced cystatin C expression and reduced the H2-DM and MHC class II ab dimer levels in DC [54].”
BackgroundDysfunction of antigen processing and presentation by dendritic cells in cancer
Bandola-Simon, J. M., & Roche, P. A. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.03.025 · Cited by 140 · see citing works
Cystatin C is a disease‐associated protein subject to multiple regulation
Xu, Y., Ding, Y., Li, X., & Wu, X. (2015) · Immunology and Cell Biology · doi:10.1038/icb.2014.121 · Cited by 116 · see citing works
“27 However, a separate study using mouse primary DCs isolated from Cst C-deficient mice demonstrated that Cst C is neither necessary nor sufficient to control MHCII expression and antigen presentation in DCs.”
BackgroundOhno, Y., Kitamura, H., Takahashi, N., Ohtake, J., Kaneumi, S., Sumida, K., Homma, S., Kawamura, H., Minagawa, N., Shibasaki, S., et al. (2016) · Cancer Immunology and Immunotherapy · doi:10.1007/s00262-015-1791-4 · Cited by 114 · see citing works
“We previously showed that IL-6 signaling suppressed major histocompatibility complex (MHC) class II expression on murine DCs via STAT3 activation, and was attenuated in CD4 T cell-mediated immune responses [13, 14].”
BackgroundSelf-citationSTAT3 in Tumor-Associated Myeloid Cells: Multitasking to Disrupt Immunity
Su, Y., Banerjee, S., White, S. V., & Kortylewski, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061803 · Cited by 123 · see citing works
Cystatin C in acute kidney injury
Bagshaw, S., & Bellomo, R. (2010) · Current Opinion in Critical Care · doi:10.1097/mcc.0b013e32833e8412 · Cited by 100 · see citing works
Stat3 as a Potential Target for Cancer Immunotherapy
Kortylewski, M., & Yu, H. (2007) · Journal of Immunotherapy · doi:10.1097/01.cji.0000211327.76266.65 · Cited by 93 · see citing works
Ansems, M., & Span, P. N. (2020) · Clinical and Translational Radiation Oncology · doi:10.1016/j.ctro.2020.04.001 · Cited by 100 · see citing works
Role of IL‐6 in dendritic cell functions
Xu, Y.-D., Cheng, M., Shang, P., & Yang, Y.-Q. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0621-616rr · Cited by 93 · see citing works
Molecular mechanisms involved in dendritic cell dysfunction in cancer
Tang, M., Diao, J., & Cattral, M. S. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2317-8 · Cited by 106 · see citing works
Regulation of suppressive function of myeloid-derived suppressor cells by CD4+ T cells
Nagaraj, S., & Gabrilovich, D. I. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.01.010 · Cited by 92 · see citing works
Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2
Mazaki, Y., Hashimoto, S., Tsujimura, T., Morishige, M., Hashimoto, A., Aritake, K., Yamada, A., Nam, J.-M., Kiyonari, H., Nakao, K., et al. (2006) · Nature Immunology · doi:10.1038/ni1349 · Cited by 86 · see citing works
Keratinocytes Determine Th1 Immunity during Early Experimental Leishmaniasis
Ehrchen, J. M., Roebrock, K., Foell, D., Nippe, N., von Stebut, E., Weiss, J. M., Münck, N., Viemann, D., Varga, G., Müller‐Tidow, C., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000871 · Cited by 69 · see citing works
“Besides, IL-6 appears to be involved in differentiation of Th17 cells and in inhibition of regulatory T-cells [48] while it also inhibited differentiation, maturation and activation of DC [49–52].”
BackgroundSOCS3 and STAT3, major controllers of the outcome of infection with Mycobacterium tuberculosis
Rottenberg, M. E., & Carow, B. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.10.004 · Cited by 84 · see citing works
Molecular characterization of interleukin-6 in the gilthead seabream (Sparus aurata).
Castellana, B., Iliev, D. B., Sepulcre, M., Mackenzie, S., Goetz, F., Mulero, V., & Planas, J. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.04.012 · Cited by 79
“Importantly, IL-6 inhibits dendritic cell maturation through STAT3 activation (Kitamura et al., 2005).”
BackgroundRoles of STAT3 in the pathogenesis and treatment of glioblastoma
Fu, W., Hou, X., Dong, L., & Hou, W. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1098482 · Cited by 90 · see citing works
“Thus, inhibition of the STAT3 pathway can promote the maturation and aggregation of DCs by inhibiting IL-10, or by inhibiting the IL6/STAT3 pathway.”
BackgroundInfluentialKang, D., Park, C.-K., Chung, C., Oh, I., Kim, Y.-C., Park, D., Kim, J., Kwon, G., Kwon, I., Sun, P., et al. (2020) · Immune Network · doi:10.4110/in.2020.20.e27 · Cited by 75 · see citing works
“Increased IL-6 signaling in the tumor microenvironment induces STAT3 activation, which inhibits Th1 cell activation by suppressing MHC class II expression in dendritic cells (12,32-34).”
BackgroundNarita, Y., Kitamura, H., Wakita, D., Sumida, K., Masuko, K., Terada, S., Nakano, K., & Nishimura, T. (2013) · Journal of Immunology · doi:10.4049/jimmunol.1103797 · Cited by 75 · see citing works
Self-citationChan, L. L. Y., Cheung, B. K. W., Li, J., & Lau, A. S. Y. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.1009659 · Cited by 72 · see citing works
Ohno, Y., Toyoshima, Y., Yurino, H., Monma, N., Xiang, H., Sumida, K., Kaneumi, S., Terada, S., Hashimoto, S., Ikeo, K., et al. (2017) · Cancer Science · doi:10.1111/cas.13330 · Cited by 74 · see citing works
Self-citationYang, D.-H., Park, J., Jin, C.-J., Kang, H.-K., Nam, J., Rhee, J., Kim, Y.-K., Chung, S.-Y., Choi, S.-J.-N., Kim, H.-J., et al. (2009) · Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis · doi:10.1016/j.leukres.2008.09.006 · Cited by 69 · see citing works
Targeting interlukin-6 to relieve immunosuppression in tumor microenvironment
Liu, Q., Yu, S.-N., Li, A.-P., Xu, H.-X., Han, X.-W., & Wu, K.-M. (2017) · Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · doi:10.1177/1010428317712445 · Cited by 68 · see citing works
Human hyper-IgE syndrome: singular or plural?
Zhang, Q., Boisson, B., Béziat, V., Puel, A., & Casanova, J.-L. (2018) · Mammalian Genome · doi:10.1007/s00335-018-9767-2 · Cited by 67 · see citing works
Toyoshima, Y., Kitamura, H., Xiang, H., Ohno, Y., Homma, S., Kawamura, H., Takahashi, N., Kamiyama, T., Tanino, M., & Taketomi, A. (2019) · Cancer immunology research · doi:10.1158/2326-6066.cir-18-0766 · Cited by 67 · see citing works
Self-citationTumor-Derived Vascular Pericytes Anergize Th Cells
Bose, A., Barik, S., Banerjee, S., Ghosh, T., Mallick, A., Majumdar, S. B., Goswami, K., Bhuniya, A., Banerjee, S., Baral, R., et al. (2013) · Journal of Immunology · doi:10.4049/jimmunol.1300280 · Cited by 66 · see citing works
Lunz, J., Specht, S., Murase, N., Isse, K., & Demetris, A. (2007) · Hepatology · doi:10.1002/hep.21906 · Cited by 66 · see citing works
Katunuma, N. (2011) · Proceedings of the Japan Academy. Series B, Physical and biological sciences · doi:10.2183/pjab.87.29 · Cited by 65
Self-citationKamon, H., Kawabe, T., Kitamura, H., Lee, J., Kamimura, D., Kaisho, T., Akira, S., Iwamatsu, A., Koga, H., Murakami, M., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601286 · Cited by 60 · see citing works
“We have shown a typical flowcytometer phenotype of DC before and after LPS stimulation (Kitamura et al, 2005).”
BackgroundSelf-citationFrick, J., Grünebach, F., & Autenrieth, I. (2010) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2009.08.010 · Cited by 63 · see citing works
Increased Cathepsin S in Prdm1−/− dendritic cells alters TFH repertoire and contributes to lupus
Kim, S. J., Schätzle, S., Ahmed, S. S., Haap, W., Jang, S., Gregersen, P., Georgiou, G., & Diamond, B. (2017) · Nature Immunology · doi:10.1038/ni.3793 · Cited by 62 · see citing works
Metcalf, J., Linders, B., Wu, S. J., Bigg, P. W., O'Donnell, P. A., Sleeper, M., Whyte, M., Haskins, M., & Ponder, K. (2009) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2009.12.003 · Cited by 59 · see citing works
“Indeed, cathepsin S expression can be activated in dendritic cells by IL-6 in a STAT-3-dependent process [57], while the human MMP-12 promoter has a STAT binding sequence [55].”
BackgroundZhou, Y.-B., Zhou, H., Li, L., Kang, Y., Cao, X., Wu, Z., Ding, L., Sethi, G., & Bian, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174202 · Cited by 57 · see citing works
Xu, Y., Schnorrer, P., Proietto, A. I., Kowalski, G. M., Febbraio, M. A., Acha‐Orbea, H., Dickins, R. A., & Villadangos, J. A. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001934 · Cited by 49 · see citing works
Ferreira, G., van Etten, E., Lage, K., Hansen, D. A., Moreau, Y., Workman, C., Waer, M., Verstuyf, A., Waelkens, E., Overbergh, L., et al. (2009) · Proteomics · doi:10.1002/pmic.200800848 · Cited by 57 · see citing works
Novel biomarkers indicating repair or progression after acute kidney injury
Kashani, K., & Kellum, J. (2015) · Current opinion in nephrology and hypertension · doi:10.1097/mnh.0000000000000090 · Cited by 56
Zhang, K., Zakeri, A., Alban, T. J., Dong, J., Ta, H. M., Zalavadia, A. H., Branicky, A., Zhao, H., Jurić, I., Husic, H., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113661 · Cited by 52 · see citing works
“77 78-81 In addition, we have unveiled that polyamines act as the key downstream effector of VISTA and causally steer myeloid differentiation; blocking polyamine production in WT monocytic progenitors curbed MDSC differentiation and induced moDC expansion, while supplementing putrescine in Vsir −/−…”
BackgroundOkuneva, O., Körber, I., Li, Z., Tian, L., Joensuu, T. H., Kopra, O., & Lehesjoki, A. (2014) · Glia · doi:10.1002/glia.22760 · Cited by 49 · see citing works
“The reduced surface expression of MHCII in Cstb2/ 2 microglia may thus be mediated by increased cathepsin activity, which has been demonstrated in cultured Cstb2/2 mouse cerebellar granule neurons (Lehtinen et al., 2009) and also in lympho- blastoid cells of EPM1 patients (Rinne et al., 1986).”
BackgroundInfluentialCytokines regulate cysteine cathepsins during TLR responses
Creasy, B., & McCoy, K. (2010) · Cellular Immunology · doi:10.1016/j.cellimm.2010.11.004 · Cited by 55 · see citing works
Targeting of Jak/STAT Pathway in Antigen Presenting Cells in Cancer
Nefedova, Y., & Gabrilovich, D. I. (2007) · Current Cancer Drug Targets · doi:10.2174/156800907780006887 · Cited by 54 · see citing works
D’Eliseo, D., Renzo, L. D., Santoni, A., & Velotti, F. (2017) · Genes & Cancer · doi:10.18632/genesandcancer.131 · Cited by 51 · see citing works
Association between serum cathepsin S and mortality in older adults.
Jobs, E., Ingelsson, E., Risérus, U., Nerpin, E., Jobs, M., Sundström, J., Basu, S., Larsson, A., Lind, L., & Ärnlöv, J. (2011) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.2011.1246 · Cited by 53 · see citing works
Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice.
Ma, X.-C., Tittiger, M., Knutsen, R. H., Kovács, A., Schaller, L., Mecham, R., & Ponder, K. (2008) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2008.03.018 · Cited by 52 · see citing works
Hirai, T., Kanda, T., Sato, K., Takaishi, M., Nakajima, K., Yamamoto, M., Kamijima, R., DiGiovanni, J., & Sano, S. (2013) · Journal of Immunology · doi:10.4049/jimmunol.1200901 · Cited by 51 · see citing works
Plasma inflammatory cytokines and survival of pancreatic cancer patients
Babic, A., Schnure, N., Neupane, N. P., Zaman, M., Rifai, N., Welch, M., Brais, L., Rubinson, D., Morales-Oyarvide, V., Yuan, C., et al. (2018) · Clinical and Translational Gastroenterology · doi:10.1038/s41424-018-0008-5 · Cited by 47 · see citing works
Molecules Involved in the Crosstalk Between Immune- and Peripheral Nerve Schwann Cells
Tzekova, N., Heinen, A., & Küry, P. (2014) · Journal of Clinical Immunology · doi:10.1007/s10875-014-0015-6 · Cited by 51 · see citing works
“Since apoE deficient Schwann cells exerted an enhanced ability to stimulate proliferation of anti-MPZ T cells, it was suggested that IL-6 diminishes the antigen presenting properties of Schwann cells [126].”
BackgroundJobs, E., Risérus, U., Ingelsson, E., Helmersson, J., Nerpin, E., Jobs, M., Sundström, J., Lind, L., Larsson, A., Basu, S., et al. (2010) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2010-0328 · Cited by 43 · see citing works
Effects of immunotherapy of IL-6 and IL-15 plasmids on transmissible venereal tumor in beagles
Chou, P.-C., Chuang, T., Jan, T., Gion, H.-C., Huang, Y.-C., Lei, H.-J., Chen, W.-Y., & Chu, R. (2009) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2009.01.002 · Cited by 47 · see citing works
Expression and function of ILTs on tolerogenic dendritic cells
Wu, J., & Horuzsko, A. (2009) · Human Immunology · doi:10.1016/j.humimm.2009.01.024 · Cited by 42
“Recently, it was discovered that the IL-6STAT3 pathway controls the intracellular MHC class II αβ dimer level through cathepsin S activity in DC [39].”
Neuwelt, A. J., Kimball, A. K., Johnson, A. M., Arnold, B. W., Bullock, B., Kaspar, R. E., Kleczko, E. K., Kwak, J., Wu, M., Heasley, L. E., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000441 · Cited by 46 · see citing works
STAT3: a potential therapeutic target in dendritic cells for the induction of transplant tolerance
Barton, B. E. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.10.3.459 · Cited by 40 · see citing works
Costantini, F., & Barbieri, G. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.05.008 · Cited by 39
Kleeman, S. O., Thakir, T. M., Demestichas, B., Mourikis, N., Loiero, D., Ferrer, M., Bankier, S., Riazat-Kesh, Y. J. R. A., Lee, H., Chantzichristos, D., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100347 · Cited by 37 · see citing works
STAT3beta, a distinct isoform from STAT3
Zhang, H., Yang, P.-L., Li, E., & Xu, L. (2019) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2019.02.006 · Cited by 45 · see citing works
Fms-like tyrosine kinase 3 ligand-dependent dendritic cells in autoimmune inflammation
Ramos, M. I. P., Tak, P. P., & Lebre, M. C. (2013) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.09.010 · Cited by 40 · see citing works
Müller, M., Fink, K., Geisel, J., Kahl, F., Jilge, B., Reimann, J., Mach, N., Autenrieth, I., & Frick, J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002376 · Cited by 37 · see citing works
Bu, L., Yu, G., Deng, W., Mao, L., Liu, J., Ma, S., Fan, T., Hall, B., Kulkarni, A. B., Zhang, W., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2015.1130206 · Cited by 40 · see citing works
Tsianakas, A., Varga, G., Barczyk, K., Bode, G., Nippe, N., Kran, N., Roth, J., Luger, T. A., Ehrchen, J. M., & Sunderkötter, C. H. (2011) · Immunobiology · doi:10.1016/j.imbio.2011.10.002 · Cited by 36 · see citing works
Zhang, Z., Chen, S., Fan, M., Ruan, G., Xi, T., Zheng, L.-F., Guo, L., Ye, F., & Xing, Y.-Y. (2021) · Helicobacter · doi:10.1111/hel.12813 · Cited by 35
Immunotherapy Using Dendritic Cells against Multiple Myeloma: How to Improve?
Nguyen-Pham, T.-N., Lee, Y., Kim, H.-J., & Lee, J.-J. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/397648 · Cited by 35
“These factors can influence the activation of STAT3 and extracellular signal-regulated kinase (ERK) phosphorylation, resulting in hyperactivation of STAT3 and ERK, which may be responsible for defective DC differentiation [60, 79].”
BackgroundCathepsin S regulates class II MHC processing in human CD4+ HLA-DR+ T cells
Costantino, C., Ploegh, H., & Hafler, D. (2009) · Journal of Immunology · doi:10.4049/jimmunol.0900921 · Cited by 35
“The enzyme activity of cathepsin B, cathepsin B plus L, cathepsin S, and asparagine endopeptidase (AEP) was measured in vitro as described (21, 22).”
MethodCysteinyl cathepsins in cardiovascular diseases
Zhang, X., Luo, S., Wang, M., & Shi, G. (2020) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2020.140360 · Cited by 36 · see citing works
Nanut, M. P., Fonović, U. P., Jakoš, T., & Kos, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.680279 · Cited by 37 · see citing works
Penafuerte, C., Feldhammer, M., Mills, J., Vinette, V., Pike, K., Hall, A., Migon, E., Karsenty, G., Pelletier, J., Zogopoulos, G., et al. (2017) · Oncoimmunology · doi:10.1080/2162402x.2017.1321185 · Cited by 33 · see citing works
Endothelial cells and cathepsins: biochemical and biomechanical regulation
Platt, M., & Shockey, W. (2015) · Biochimie · doi:10.1016/j.biochi.2015.10.010 · Cited by 33 · see citing works
Regulation of CD4 T‐cell receptor diversity by vaccine adjuvants
Baumgartner, C., & Malherbe, L. (2010) · Immunology · doi:10.1111/j.1365-2567.2010.03265.x · Cited by 33 · see citing works
Ielpo, S., Barberini, F., Moghaddam, F. D., Pesce, S., Cencioni, C., Spallotta, F., Ninno, A. D., Businaro, L., Marcenaro, E., Bei, R., et al. (2024) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2024.102843 · Cited by 32 · see citing works
In vivo induction of regulatory T cells for immune tolerance in hemophilia
Wang, X., Terhorst, C., & Herzog, R. W. (2015) · Cellular Immunology · doi:10.1016/j.cellimm.2015.10.001 · Cited by 37 · see citing works
Bae, G., Kim, J., Park, K., Koo, B. S., Jo, I., Choi, S.-B., Lee, C. H., Jung, W., Cho, J., Hong, S., et al. (2012) · Phytotherapy Research · doi:10.1002/ptr.4649 · Cited by 38 · see citing works
“Bone-marrow-derived DCs. Bone-marrow-derived DCs (BMDCs) were generated as previously described (Kitamura et al., 2005).”
MethodSelf-citationOncostatin M Receptor-β Signaling Limits Monocytic Cell Recruitment in Acute Inflammation1
Hams, E., Colmont, C. S., Dioszeghy, V., Hammond, V., Fielding, C., Williams, A., Tanaka, M., Miyajima, A., Taylor, P., Topley, N., et al. (2008) · Journal of Immunology · doi:10.4049/jimmunol.181.3.2174 · Cited by 32 · see citing works
Ghorbaninezhad, F., Asadzadeh, Z., Masoumi, J., Mokhtarzadeh, A., Kazemi, T., Maleki, L. A., Shotorbani, S. S., Shadbad, M. A., Baghbanzadeh, A., Hemmat, N., et al. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120466 · Cited by 32 · see citing works
PMMA particle-mediated DNA vaccine for cervical cancer.
Lou, P., Cheng, W.-F., Chung, Y.-C., Cheng, C.-Y., Chiu, L., & Young, T. (2009) · Journal of Biomedical Materials Research. Part A · doi:10.1002/jbm.a.31919 · Cited by 31
Tumor secretome shapes the immune landscape during cancer progression
Yang, J.-Q., Tang, S., Saba, N., Shay, C., & Teng, Y. (2025) · Journal of experimental & clinical cancer research : CR · doi:10.1186/s13046-025-03302-0 · Cited by 30 · see citing works
Ganesh, S., Kim, M. J., Lee, J., Feng, X., Ule, K., Mahan, A. L., Krishnan, H. S., Wang, Z., Anzahaee, M. Y., Singhal, G., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.03.035 · Cited by 31 · see citing works
“31,32 Hyperactivation of STAT3 in MDSCs, M2 macrophages, and Tregs impairs the production of pro-in fl ammatory mediators such as interferon-g , augments the release of tolerogenic mediators, and drives increased expression of immune checkpoint molecules to inhibit effector cell responses.”
Cheng, X.-W., Narisawa, M., Wang, H.-L., & Piao, L.-M. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01040-4 · Cited by 29 · see citing works
- Authors
- Kitamura, H., Kamon, H., Sawa, S.-I., Park, S.-J., Katunuma, N., Ishihara, K., Murakami, M., & Hirano, T.
- Affiliations
- RIKEN (JP)
- The University of Osaka (JP)
- Tokushima Bunri University (JP)
- Corresponding author
- Hirano, Toshio
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 23
- Issue
- 5
- Pages
- 491-502
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2074991167
- Cited by
- 223
- References
- 0
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 11 · 2021: 18 · 2020: 13 · 2019: 13 · 2018: 14 · 2017: 11 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 13 · 2012: 10
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-6/STAT3 signaling, cathepsin S, dendritic cells, cystatin C, Ii, T cell activation, gp130, LPS, antigen presentation, CD4+ T cells, immunosuppression
- MeSH terms
- Animals, Histocompatibility Antigens Class II, Cathepsins, Cells, Cultured, Dendritic Cells, Lymphocyte Activation, Mice, Transgenic, RNA, Messenger, Signal Transduction, CD4-Positive T-Lymphocytes, Interleukin-6, Up-Regulation, Cystatins, Dimerization, STAT3 Transcription Factor, Mice
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