Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells
Open accessAbstract
Interleukin (IL)-4 is the most potent factor that causes naive CD4+ T cells to differentiate to the T helper cell (Th) 2 phenotype, while IL-12 and interferon γ trigger the differentiation of Th1 cells. However, the source of the initial polarizing IL-4 remains unclear. Here, we show that IL-6, probably secreted by antigen-presenting cells, is able to polarize naive CD4+ T cells to effector Th2 cells by inducing the initial production of IL-4 in CD4+ T cells. These results show that the nature of the cytokine (IL-12 or IL-6), which is produced by antigen-presenting cells in response to a particular pathogen, is a key factor in determining the nature of the immune response.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IL-6 directs the differentiation of IL-4-producing Th2 cells, while it inhibits the differentiation of IFNγ-producing Th1 cells.
“In addition to the aforementioned role of IL-6 on Tfh cells, IL-6 is known to direct the differentiation of IL-4-producing T helper type 2 (Th2) cells, while it inhibits the differentiation of IFNγ-producing Th1 cells (155).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [155]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
Hsieh, C.-S., Macatonia, S. E., Tripp, C. S., Wolf, S. F., O'Garra, A., & Murphy, K. M. (1993) · Science · doi:10.1126/science.8097338 · Cited by 3,134 · see citing works
IL-10 inhibits cytokine production by activated macrophages
Fiorentino, D. F., Zlotnik, A., Mosmann, T. R., Howard, M., & O’Garra, A. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.11.3815 · Cited by 2,888 · see citing works
Van Snick, J. (1990) · Annual Review of Immunology · doi:10.1146/annurev.iy.08.040190.001345 · Cited by 1,890 · see citing works
Lymphocyte responses and cytokines
Paul, W. E., & Seder, R. A. (1994) · Cell · doi:10.1016/0092-8674(94)90332-8 · Cited by 1,832 · see citing works
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768 · cited 1× · see citing works
“In correlation with the previous characterization of IL-62/2 mice (32, 33), analysis of cellular populations in the spleen”
Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.
Cao, Z., Umek, R. M., & McKnight, S. L. (1991) · Genes & Development · doi:10.1101/gad.5.9.1538 · Cited by 1,663 · see citing works
Kuchroo, V. K., Das, M. P., Brown, J. A., Ranger, A. M., Zamvil, S. S., Sobel, R. A., Weiner, H. L., Nabavi, N., & Glimcher, L. H. (1995) · Cell · doi:10.1016/0092-8674(95)90349-6 · Cited by 1,642 · see citing works
A nuclear factor for IL‐6 expression (NF‐IL6) is a member of a C/EBP family.
Akira, S., Isshiki, H., Sugita, T., Tanabe, O., Kinoshita, S. M., Nishio, Y., Nakajima, T., Hirano, T., & Kishimoto, T. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb08316.x · Cited by 1,446 · see citing works
Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130
Taga, T., Hibi, M., Hirata, Y., Yamasaki, K., Yasukawa, K., Matsuda, T., Hirano, T., & Kishimoto, T. (1989) · Cell · doi:10.1016/0092-8674(89)90438-8 · Cited by 1,396 · see citing works
D’Andrea, A., Aste-Amézaga, M., Valiante, N. M., Ma, X., Kubin, M. Z., & Trinchieri, G. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.3.1041 · Cited by 1,367 · see citing works
Molecular cloning and expression of an IL-6 signal transducer, gp130
Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T., & Kishimoto, T. (1990) · Cell · doi:10.1016/0092-8674(90)90411-7 · Cited by 1,304 · see citing works
IL‐4 directs the development of Th2‐like helper effectors
Swain, S. L., Weinberg, A. D., English, M., & Huston, G. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.145.11.3796 · Cited by 1,254 · see citing works
D’Andrea, A., Rengaraju, M., Valiante, N. M., Chehimi, J., Kubin, M. Z., Aste-Amézaga, M., Chan, S. H., Kobayashi, M., Young, D., & Nickbarg, E. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.5.1387 · Cited by 1,143 · see citing works
Production of hybridoma growth factor by human monocytes
Aarden, L. A., de Groot, E. R., Schaap, O. L., & Lansdorp, P. M. (1987) · European Journal of Immunology · doi:10.1002/eji.1830171004 · Cited by 1,091 · see citing works
Cloning and Expression of the Human Interleukin-6 (BSF-2/IFNβ 2) Receptor
Yamasaki, K., Taga, T., Hirata, Y., Yawata, H., Kawanishi, Y., Seed, B., Taniguchi, T., Hirano, T., & Kishimoto, T. (1988) · Science · doi:10.1126/science.3136546 · Cited by 1,061 · see citing works
Seder, R. A., Gazzinelli, R. T., Sher, A., & Paul, W. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.21.10188 · Cited by 976 · see citing works
Le Gros, G., Ben-Sasson, S. Z., Seder, R., Finkelman, F. D., & Paul, W. E. (1990) · The Journal of experimental medicine · doi:10.1084/jem.172.3.921 · Cited by 954 · see citing works
Gearing, D. P., Comeau, M. R., Friend, D. J., Gimpel, S. D., Thut, C. J., McGourty, J., Brasher, K. K., King, J. A., Gillis, S. A., Mosley, B., et al. (1992) · Science · doi:10.1126/science.1542794 · Cited by 889 · see citing works
Interleukin-6 and Its Receptor: A Paradigm for Cytokines
Kishimoto, T., Akira, S., & Taga, T. (1992) · Science · doi:10.1126/science.1411569 · Cited by 883 · see citing works
Yoshimoto, T., & Paul, W. E. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.4.1285 · Cited by 841 · see citing works
Tripp, C. S., Wolf, S. F., & Unanue, E. R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3725 · Cited by 768 · see citing works
Interleukin‐6 deficient mice are protected from bone loss caused by estrogen depletion.
Poli, V., Balena, R. F., Fattori, E., Markatos, A., Yamamoto, M., Tanaka, H., Ciliberto, G., Rodan, G. A., & Costantini, F. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06368.x · Cited by 745 · see citing works
Constant, S. L., Pfeiffer, C., Woodard, A., Pasqualini, T., & Bottomly, K. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.5.1591 · Cited by 677 · see citing works
Kaye, J. G., Hsu, M.-L., Sauron, M.-E., Jameson, S. C., Gascoigne, N. R. J., & Hedrick, S. Μ. (1989) · Nature · doi:10.1038/341746a0 · Cited by 632 · see citing works
Poli, V., Mancini, F. P., & Cortese, R. (1990) · Cell · doi:10.1016/0092-8674(90)90459-r · Cited by 598 · see citing works
Lenschow, D. J., Ho, S. C., Sattar, H. A., Rhee, L., Gray, G. S., Nabavi, N., Herold, K. C., & Bluestone, J. A. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.3.1145 · Cited by 582 · see citing works
Nakajima, T., Kinoshita, S. M., Sasagawa, T., Sasaki, K., Naruto, M., Kishimoto, T., & Akira, S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.6.2207 · Cited by 578 · see citing works
Descombes, P., Chojkier, M., Lichtsteiner, S., Falvey, E., & Schibler, U. (1990) · Genes & Development · doi:10.1101/gad.4.9.1541 · Cited by 575 · see citing works
Bretscher, P. A., Wei, G., Menon, J. N., & Bielefeldt‐Ohmann, H. (1992) · Science · doi:10.1126/science.1636090 · Cited by 499 · see citing works
Nuclear factor of activated T cells contains Fos and Jun
Jain, J., McCaffrey, P. G., Valge-archer, V. E., & Rao, A. (1992) · Nature · doi:10.1038/356801a0 · Cited by 497 · see citing works
Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo.
Pfeiffer, C., Stein, J., Southwood, S., Ketelaar, H., Sette, A., & Bottomly, K. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.4.1569 · Cited by 388 · see citing works
Romani, L., Mencacci, A., Cenci, E., Spaccapelo, R., Toniatti, C., Puccetti, P., Bistoni, F., & Poli, V. (1996) · Journal of Experimental Medicine · doi:10.1084/jem.183.4.1345 · Cited by 351 · see citing works
Northrop, J. P., Ullman, K. S., & Crabtree, G. R. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53861-8 · Cited by 345 · see citing works
Dalrymple, S., Lucian, L., Slattery, R., McNeil, T., Aud, D., Fuchino, S., Lee, F., & Murray, R. (1995) · Infection and Immunity · doi:10.1128/iai.63.6.2262-2268.1995 · Cited by 330 · see citing works
Constructing polycompetitor cDNAs for quantitative PCR
Reiner, S. L., Zheng, S., Corry, D. B., & Locksley, R. M. (1993) · Journal of Immunological Methods · doi:10.1016/0022-1759(93)90104-f · Cited by 312 · see citing works
Molecular Cloning of a Transcription Factor, AGP/EBP, That Belongs to Members of the C/EBP Family
Chang, C., Chen, T. T., Lei, H., Chen, D., & Lee, S.-C. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.12.6642 · Cited by 264 · see citing works
Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction.
Yin, T., Taga, T., Tsang, M., Yasukawa, K., Kishimoto, T., & Yang, Y. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.5.2555 · Cited by 262 · see citing works
Seder, R. A., Paul, W. E., Dvořàk, A. M., Sharkis, S. J., Kagey‐Sobotka, A., Niv, Y., Finkelman, F. D., Barbieri, S. A., Galli, S. J., & Plaut, M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.7.2835 · Cited by 257 · see citing works
Kamogawa, Y., Minasi, L. A. E., Carding, S. R., Bottomly, K., & Flavell, R. A. (1993) · Cell · doi:10.1016/0092-8674(93)90542-x · Cited by 257 · see citing works
Self-citationCoordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene
Rooney, J. W., Hoey, T. C., & Glimcher, L. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90028-4 · Cited by 255 · see citing works
Szabo, S. J., Gold, J. S., Murphy, T. L., & MURPHY, K. M. M. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.8.4793 · Cited by 240 · see citing works
The NFAT-1 DNA Binding Complex in Activated T Cells Contains Fra-1 and JunB
Boise, L., Petryniak, B., Mao, X., June, C. H., Wang, C.-Y., Lindsten, T., Bravo, R., Kovary, K., Leiden, J. M., & Thompson, C. B. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.3.1911-1919.1993 · Cited by 216 · see citing works
Taga, T., Narazaki, M., Yasukawa, K., Saito, T., Miki, D., Hamaguchi, M., Davis, S. H., SHOYAB, M., Yancopoulos, G. D., & Kishimoto, T. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10998 · Cited by 198 · see citing works
Chuvpilo, S. A., Schomberg, C., Gerwig, R., Heinfling, A., Reeves, R., Grummt, F., & ling, E. S. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.24.5694 · Cited by 186 · see citing works
Transcription of the interleukin 4 gene is regulated by multiple promoter elements.
Todd, M., Grusby, M. J., Lederer, J. A., Lacy, E., Lichtman, A. H., & Glimcher, L. H. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.6.1663 · Cited by 101 · see citing works
Bradley, L. M., Duncan, D. D., Yoshimoto, K., & Swain, S. L. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.8.3119 · Cited by 98 · see citing works
Nuclear factor-IL6 activates the human IL-4 promoter in T cells
Davydov, I. V., Krammer, P. H., & Li-Weber, M. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.11.5273 · Cited by 85 · see citing works
High- and low-affinity receptors for murine interleukin 6. distinct distribution on b and t cells
Coulie, P. G., Stevens, M., & Snick, J. V. (1989) · European Journal of Immunology · doi:10.1002/eji.1830191121 · Cited by 83 · see citing works
Szabo, S. J., Gold, J. S., Murphy, T. L., & MURPHY, K. M. M. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.8.4793-4805.1993 · Cited by 62 · see citing works
Molecular dissection of the mouse interleukin-4 promoter.
Bruhn, K. W., Nelms, K. A., Boulay, J., Paul, W. E., & Lenardo, M. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9707 · Cited by 58 · see citing works
Flagged first, then by citations
3 of the 55 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- [1]Paul WE Seder RA Lymphocyte response and cytokines Cell 1994 76 241 251 7904900
- [7]Hsieh CS Macatonia SE Tripp CS Wolf SF O'Garra A Murphy KM Development of Th1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages Science (Wash DC) 1993 260 547 549 8097338
- [17]Chomczynski P Sacchi N Single-step method of RNA extraction by acid guanidinium thiocyanate-phenolchloroform Anal Biochem 1987 162 156 159 2440339
- [25]Yamasaki K Taga T Hirata Y Yawata H Kawanishi Y See B Tanaiguchi T Hirano T Kishimoto T Cloning and expression of human interleukin-6 Science (Wash DC) 1988 241 825 828 3136546
Cited by
Sorted by citations
Immunobiology of Dendritic Cells
Banchereau, J., Brière, F., Caux, C., Davoust, J. M., Lebecque, S., Liu, Y., Pulendran, B., & Palucka, K. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.767 · Cited by 6,612 · see citing works
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729 · see citing works
IL-6 as a keystone cytokine in health and disease
Hunter, C. A., & Jones, S. A. (2015) · Nature Immunology · doi:10.1038/ni.3153 · Cited by 2,511 · see citing works
Zheng, W.-P., & Flavell, R. A. (1997) · Cell · doi:10.1016/s0092-8674(00)80240-8 · Cited by 2,384 · see citing works
Self-citationREGULATION OF IMMUNE RESPONSES BY TGF-β
Letterio, J. J., & Roberts, A. B. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.137 · Cited by 1,894 · see citing works
CD40 AND CD154 IN CELL-MEDIATED IMMUNITY
Grewal, I. S., & Flavell, R. A. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.111 · Cited by 1,538 · see citing works
Self-citationCytokines Induce the Development of Functionally Heterogeneous T Helper Cell Subsets
O’Garra, A. (1998) · Immunity · doi:10.1016/s1074-7613(00)80533-6 · Cited by 1,535 · see citing works
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases
Shi, Y., Wang, Y., Li, Q., Liu, K., Hou, J., Shao, C., & Wang, Y. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0023-5 · Cited by 1,223 · see citing works
The immunobiology of schistosomiasis
Pearce, E. J., & MacDonald, A. S. (2002) · Nature reviews. Immunology · doi:10.1038/nri843 · Cited by 1,151 · see citing works
Dendritic cell regulation of TH1-TH2 development
Moser, M., & MURPHY, K. M. M. (2000) · Nature Immunology · doi:10.1038/79734 · Cited by 1,106 · see citing works
Romagnani, S. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)80019-9 · Cited by 1,063 · see citing works
Molecular Mechanisms RegulatinG Th1 Immune Responses
Szabo, S. J., Sullivan, B. M., Peng, S. L., & Glimcher, L. H. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.140942 · Cited by 1,021 · see citing works
Distinct dendritic cell subsets differentially regulate the class of immune response in vivo
Pulendran, B., Smith, J. L., Caspary, G., Brasel, K., Pettit, D., Maraskovsky, E., & Maliszewski, C. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.3.1036 · Cited by 993 · see citing works
IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines
Molet, S., Hamid, Q. A., Davoineb, F., Nutku, E., Tahaa, R., Pagé, N., Olivenstein, R., Elias, J. A., & Chakir, J. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.117929 · Cited by 954 · see citing works
Christensen, H. R., Frøkiær, H., & Pestka, J. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.1.171 · Cited by 905 · see citing works
Amsen, D., Blander, J. M., Lee, G. R., Tanigaki, K., Honjo, T., & Flavell, R. A. (2004) · Cell · doi:10.1016/s0092-8674(04)00451-9 · Cited by 902 · see citing works
Self-citationChemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses
Sallusto, F., Lanzavecchia, A., & Mackay, C. R. (1998) · Immunology Today · doi:10.1016/s0167-5699(98)01346-2 · Cited by 888 · see citing works
The two faces of IL-6 on Th1/Th2 differentiation
Diehl, S. A., & Rincón, M. (2002) · Molecular Immunology · doi:10.1016/s0161-5890(02)00210-9 · Cited by 873 · see citing works
Self-citationDirecting Transition from Innate to Acquired Immunity: Defining a Role for IL-6
Jones, S. A. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.6.3463 · Cited by 771 · see citing works
Fallon, P. G., Ballantyne, S. J., Mangan, N. E., Barlow, J. L., Dasvarma, A., Hewett, D. R., McIlgorm, A., Jolin, H. E., & McKenzie, A. N. J. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051615 · Cited by 738 · see citing works
Elias, J. A., Zhu, Z., Chupp, G. L., & Homer, R. (1999) · Journal of Clinical Investigation · doi:10.1172/jci8124 · Cited by 706 · see citing works
Stat6-Independent GATA-3 Autoactivation Directs IL-4-Independent Th2 Development and Commitment
Ouyang, W., Löhning, M., Gao, Z., Assenmacher, M., Ranganath, S. H., Radbruch, A., & MURPHY, K. M. M. (2000) · Immunity · doi:10.1016/s1074-7613(00)80156-9 · Cited by 702 · see citing works
The development of inflammatory TH-17 cells requires interferon-regulatory factor 4
Brüstle, A., Heink, S., Huber, M., Rosenplänter, C., Stadelmann, C., Yu, P., Arpaia, E., Mak, T. W., Kamradt, T., & Lohoff, M. D. (2007) · Nature Immunology · doi:10.1038/ni1500 · Cited by 691 · see citing works
Hayden, F. G., Fritz, R., Lobo, M. C., Alvord, W. G., Strober, W., & Straus, S. E. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1355 · Cited by 680 · see citing works
IL-6 signal transduction and its physiological roles: the signal orchestration model
Kamimura, D., Ishihara, K., & Hirano, T. (2003) · Reviews of Physiology, Biochemistry and Pharmacology · doi:10.1007/s10254-003-0012-2 · Cited by 673 · see citing works
Rose‐John, S., Scheller, J., Elson, G., & Jones, S. A. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.1105674 · Cited by 647 · see citing works
Interleukin-6: designing specific therapeutics for a complex cytokine
Garbers, C., Heink, S., Korn, T., & Rose-John, S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.45 · Cited by 643 · see citing works
Role of IL-6 in Asthma and Other Inflammatory Pulmonary Diseases
Rincón, M., & Irvin, C. G. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4874 · Cited by 622 · see citing works
Self-citationLineage commitment in the immune system: the T helper lymphocyte grows upPreprint
Glimcher, L. H., & MURPHY, K. M. M. (2000) · Genes & Development · doi:10.1101/gad.14.14.1693 · Cited by 624 · see citing works
Microbial lipopeptides induce the production of IL-17 in Th cells
Infante-Duarte, C., Horton, H. F., Byrne, M. C., & Kamradt, T. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.11.6107 · Cited by 586 · see citing works
IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer
Neurath, M. F., & Finotto, S. (2011) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2011.02.003 · Cited by 578 · see citing works
Interleukin-6 Exacerbates Early Atherosclerosis in Mice
Huber, S. A., Sakkinen, P. A., Conze, D. B., Hardin, N. J., & Tracy, R. P. (1999) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.19.10.2364 · Cited by 549 · see citing works
The effects of IL-6 on CD4 T cell responses
Dienz, O., & Rincón, M. (2008) · Clinical Immunology · doi:10.1016/j.clim.2008.08.018 · Cited by 529 · see citing works
Self-citationInterleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update
Su, H., Lei, C., & Zhang, C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00405 · Cited by 525 · see citing works
An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus
Rabinovitch, A. (1998) · Diabetes/Metabolism Reviews · doi:10.1002/(sici)1099-0895(199806)14:2 · Cited by 456 · see citing works
Kurowska‐Stolarska, M., Kewin, P., Murphy, G., Russo, R. C., Stolarski, B., Garcia, C. C., Komai‐Koma, M., Pitman, N. I., Li, Y., McKenzie, A. N. J., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.7.4780 · Cited by 461 · see citing works
Differentiation of CD4+ T Cells to Th1 Cells Requires MAP Kinase JNK2
Yang, D. D., Conze, D. B., Whitmarsh, A. J., Barrett, T., Davis, R. J., Rincón, M., & Flavell, R. A. (1998) · Immunity · doi:10.1016/s1074-7613(00)80640-8 · Cited by 453 · see citing works
Self-citationImprovement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy
Nishimoto, N., Sasai, M., Shima, Y., Nakagawa, M., Matsumoto, T., Shirai, T., Kishimoto, T., & Yoshizaki, K. (2000) · Blood · doi:10.1182/blood.v95.1.56.001k13_56_61 · Cited by 445 · see citing works
Dienz, O., Eaton, S. M., Bond, J. P., Neveu, W. A., Moquin, D., Noubade, R., Briso, E. M., Charland, C., Leonard, W. J., Ciliberto, G., et al. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20081571 · Cited by 440 · see citing works
Self-citationInterferon‐γ expression by Th1 effector T cells mediated by the p38 MAP kinase signaling pathway
Rincón, M., Enslen, H., Raingeaud, J., Recht, M., Zapton, T., Su, M. S., Penix, L. A., Davis, R. J., & Flavell, R. A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.10.2817 · Cited by 419 · see citing works
Self-citationInhibition of Th1 Differentiation by IL-6 Is Mediated by SOCS1
Diehl, S. A., Anguíta, J., Hoffmeyer, A., Zapton, T., Ihle, J. N., Fikrig, E., & Rincón, M. (2000) · Immunity · doi:10.1016/s1074-7613(00)00078-9 · Cited by 402 · see citing works
Self-citationIL-33–activated dendritic cells induce an atypical TH2-type response
Rank, M. A., Kobayashi, T., Kozaki, H., Bartemes, K. R., Squillace, D. L., & Kita, H. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.02.026 · Cited by 395 · see citing works
Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch
Amsen, D., Antov, A., Jankovic, D., Sher, A., Radtke, F., Souabni, A., Busslinger, M., McCright, B., Gridley, T., & Flavell, R. A. (2007) · Immunity · doi:10.1016/j.immuni.2007.05.021 · Cited by 396 · see citing works
Self-citationImpaired Development of Th2 Cells in IL-13-Deficient Mice
McKenzie, G. J., Emson, C. L., Bell, S. E., Anderson, S. M., Fallon, P. G., Zurawski, G., Murray, R., Grencis, R. K., & McKenzie, A. N. J. (1998) · Immunity · doi:10.1016/s1074-7613(00)80625-1 · Cited by 381 · see citing works
Interleukin-6 Signaling Drives Fibrosis in Unresolved Inflammation
Fielding, C. A., Jones, G. W., McLoughlin, R. M., McLeod, L., Hammond, V. J., Fernandez, J. U., Williams, A. S., Lambie, M., Foster, T. L., Liao, C., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.10.022 · Cited by 372 · see citing works
Distinct Profiles of Human B Cell Effector Cytokines: A Role in Immune Regulation?1
Duddy, M., Alter, A., & Bar-Or, A. (2004) · Journal of Immunology · doi:10.4049/jimmunol.172.6.3422 · Cited by 393 · see citing works
Signaling mechanisms through gp130: A model of the cytokine system
Hirano, T., Nakajima, K., & Hibi, M. (1997) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(98)80005-1 · Cited by 370 · see citing works
Lethal tuberculosis in interleukin-6-deficient mutant mice
Ladel, C. H., Blum, C., Dreher, A., Reifenberg, K., Köpf, M., & Kaufmann, S. H. E. (1997) · Infection and Immunity · doi:10.1128/iai.65.11.4843-4849.1997 · Cited by 358 · see citing works
Kool, M., Willart, M. A. M., van Nimwegen, M., Bergen, I. M., Pouliot, P., Virchow, J. C., Jr., Rogers, N. C., Osorio, F., Sousa, C. R. E., Hammad, H., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.015 · Cited by 360 · see citing works
Mechanism of action of clinically approved adjuvants
Lambrecht, B. N., Kool, M., Willart, M. A. M., & Hammad, H. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.01.004 · Cited by 354 · see citing works
Flynn, S., Toellner, K.-M., Raykundalia, C., Goodall, M., & Lane, P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.2.297 · Cited by 351 · see citing works
Cytokines and HIV-1: Interactions and Clinical Implications
Kedzierska, K., & Crowe, S. M. (2001) · Antiviral chemistry & chemotherapy · doi:10.1177/095632020101200301 · Cited by 350 · see citing works
Noben-Trauth, N., Shultz, L. D., Brombacher, F., Urban, J. F., Gu, H., & Paul, W. E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10838 · Cited by 344 · see citing works
Doganci, A., Eigenbrod, T., Krug, N., Sanctis, G. T. D., Hausding, M., Erpenbeck, V. J., Haddad, E., Schmitt, E., Bopp, T., Kallen, K.-J., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22433 · Cited by 334 · see citing works
Beale, J., Jayaraman, A., Jackson, D. J., Macintyre, J. D. R., Edwards, M. R., Walton, R. P., Zhu, J., Ching, Y. M., Shamji, B., Edwards, M., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009124 · Cited by 332 · 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
Interleukin-4 and lnterleukin-13: Their Similarities and Discrepancies
Chomarat, P., & Banchereau, J. (1998) · International Reviews of Immunology · doi:10.3109/08830189809084486 · Cited by 331 · see citing works
Interleukin-6: from an inflammatory marker to a target for inflammatory diseases
Rincón, M. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.07.003 · Cited by 328 · see citing works
Self-citationBasophils enhance immunological memory responses
Denzel, A., Maus, U. A., Gomez, M. R., Moll, C., Niedermeier, M., Winter, C., Maus, R., Hollingshead, S. K., Briles, D. E., Kunz‐Schughart, L. A., et al. (2008) · Nature Immunology · doi:10.1038/ni.1621 · Cited by 327 · see citing works
Dust Mite Proteolytic Allergens Induce Cytokine Release from Cultured Airway Epithelium
King, C., Brennan, S., Thompson, P. J., & Stewart, G. A. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.7.3645 · Cited by 323 · see citing works
The paradigm of Th1 and Th2 cytokines
Singh, V. K., Mehrotra, S., & Agarwal, S. S. (1999) · Immunologic Research · doi:10.1007/bf02786470 · Cited by 318 · see citing works
Resolution of inflammation in bone regeneration: From understandings to therapeutic applications
Newman, H., Shih, Y.-R. V., & Varghese, S. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121114 · Cited by 318 · see citing works
Fibrosis—a lethal component of systemic sclerosis
Ho, Y. Y., Lagares, D., Tager, A. M., & Kapoor, M. (2014) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2014.53 · Cited by 307 · see citing works
Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation
Randolph, D. A., Stephens, R., Carruthers, C. J. L., & Chaplin, D. (1999) · Journal of Clinical Investigation · doi:10.1172/jci7631 · Cited by 301 · see citing works
Doganci, A., Eigenbrod, T., Krug, N., Sanctis, G. T. D., Hausding, M., Erpenbeck, V. J., Haddad, E., Schmitt, E., Bopp, T., Kallen, K.-J., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522433 · Cited by 304 · see citing works
KNOLLE, P., SCHMITT, E., JIN, S., GERMANN, T., DUCHMANN, R., HEGENBARTH, S., GERKEN, G., & LOHSE, A. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70508-1 · Cited by 298 · see citing works
The Key Role of Macrophages in the Immunopathogenesis of Inflammatory Bowel Disease
Mahida, Y. R. (2000) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200002000-00004 · Cited by 293 · see citing works
Dunford, P. J., O'Donnell, N., Riley, J. P., Williams, K. N., Karlsson, L., & Thurmond, R. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.11.7062 · Cited by 290 · see citing works
Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells.
Conze, D. B., Weiss, L., Regen, P. S., Bhushan, A., Weaver, D. L., Johnson, P. F., & Rincón, M. (2001) · PubMed · Cited by 282 · see citing works
Self-citationVascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α
Wang, Q., He, Z., Huang, M., Liu, T., Wang, Y., Xu, H., Duan, H., Ma, P., Zhang, L., Zamvil, S. S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03050-0 · Cited by 279 · see citing works
Spencer, L. A., Szela, C. T., Perez, S. A. C., Kirchhoffer, C. L., Neves, J. S., Radke, A. L., & Weller, P. F. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0108058 · Cited by 274 · see citing works
Ohshima, Y., Yang, L., Uchiyama, T., Tanaka, Y., Baum, P. R., Sergerie, M., Hermann, P., & Delespesse, G. (1998) · Blood · doi:10.1182/blood.v92.9.3338.421k19_3338_3345 · Cited by 268 · see citing works
Yip, H. C., Karulin, A. Y., Tary‐Lehmann, M., Hesse, M. D., Radeke, H. H., Heeger, P. S., Trezza, R. P., Heinzel, F. P., Forsthuber, T. G., & Lehmann, P. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.3942 · Cited by 259 · see citing works
Signaling pathways in Th2 development
Mowen, K. A., & Glimcher, L. H. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00209.x · Cited by 255 · see citing works
gp130 at the nexus of inflammation, autoimmunity, and cancer
Silver, J. S., & Hunter, C. A. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.0410217 · Cited by 252 · see citing works
Laino, A. S., Woods, D. M., Vassallo, M., Qian, X., Tang, H., Wind‐Rotolo, M., & Weber, J. S. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000842 · Cited by 254 · see citing works
Consequences of regulated pre-mRNA splicing in the immune system
Lynch, K. W. (2004) · Nature reviews. Immunology · doi:10.1038/nri1497 · Cited by 246 · see citing works
Ulanova, M., Tarkowski, A., Hahn‐Zoric, M., & Hanson, L. Å. (2001) · Infection and Immunity · doi:10.1128/iai.69.2.1151-1159.2001 · Cited by 239 · see citing works
Antigen-specific regulatory T cells—their induction and role in infection
Mills, K. H. G., & McGuirk, P. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2003.12.006 · Cited by 236 · see citing works
Cytokines: Past, Present, and Future
Oppenheim, J. J. (2001) · International Journal of Hematology · doi:10.1007/bf02982543 · Cited by 236 · see citing works
Murata, Y., Shimamura, T., & Hamuro, J. (2002) · International Immunology · doi:10.1093/intimm/14.2.201 · Cited by 232 · see citing works
Epithelial cells and airway diseases
Proud, D., & Leigh, R. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01033.x · Cited by 228 · see citing works
T cells in systemic sclerosis: a reappraisal
O'Reilly, S., Hugle, T., & van Laar, J. M. (2012) · Rheumatology · doi:10.1093/rheumatology/kes090 · Cited by 218 · see citing works
Titus, R. G., Bishop, J. V., & Mejia, J. S. (2006) · Parasite Immunology · doi:10.1111/j.1365-3024.2006.00807.x · Cited by 218 · see citing works
Chiaramonte, M. G., Schopf, L. R., Neben, T. Y., Cheever, A. W., Donaldson, D. D., & Wynn, T. A. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.2.920 · Cited by 216 · see citing works
Eosinophils and Th2 immunity: contemporary insights
Spencer, L. A., & Weller, P. F. (2010) · Immunology and Cell Biology · doi:10.1038/icb.2009.115 · Cited by 213 · see citing works
Immunoregulation by capsular components of Cryptococcus neoformans
Vecchiarelli, A. (2000) · Medical Mycology · doi:10.1080/mmy.38.6.407.417 · Cited by 213 · see citing works
Huber, S. A., Sakkinen, P. A., David, C. S., Newell, M. K., & Tracy, R. P. (2001) · Circulation · doi:10.1161/01.cir.103.21.2610 · Cited by 212 · see citing works
Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma
Krishnamoorthy, N., Oriss, T. B., Paglia, M., Fei, M., Yarlagadda, M., Vanhaesebroeck, B., Ray, A., & Ray, P. (2008) · Nature Medicine · doi:10.1038/nm1766 · Cited by 212 · see citing works
Interleukin 6 and Rheumatoid Arthritis
Yoshida, Y., & Tanaka, T. (2014) · BioMed Research International · doi:10.1155/2014/698313 · Cited by 207 · see citing works
Spencer, S., Bal, S. K., Egner, W., Allen, H. L., Raza, S. I., Ma, C. A., Gürel, M., Zhang, Y., Sun, G., Sabroe, R. A., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190344 · Cited by 206 · see citing works
Treatment of allergic asthma: Modulation of Th2 cells and their responses
Bošnjak, B., Stelzmueller, B., Erb, K. J., & Epstein, M. M. (2011) · Respiratory Research · doi:10.1186/1465-9921-12-114 · Cited by 205 · see citing works
Fortin, P. R., Clarke, A. E., Joseph, L., Liang, M. H., Tänzer, M., Ferland, D., Phillips, C., Partridge, A. J., B�lisle, P., Fossel, A. H., et al. (1999) · Arthritis & Rheumatism · doi:10.1002/1529-0131(199908)42:8 · Cited by 708 · see citing works
Induction of NFATc2 Expression by Interleukin 6 Promotes T Helper Type 2 Differentiation
Diehl, S. A., Chow, C.-W., Weiss, L., Palmetshofer, A., Twardzik, T., Rounds, L., Serfling, E., Davis, R. J., Anguíta, J., & Rincón, M. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020026 · Cited by 199 · see citing works
Self-citationKöpf, M., Herren, S., Wiles, M. V., Pepys, M. B., & Kosco‐Vilbois, M. H. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.10.1895 · Cited by 197 · see citing works
Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes
Barrett, N. A., Rahman, O. M., Fernandez, J. M., Parsons, M. W., Xing, W., Austen, K. F., & Kanaoka, Y. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20100793 · Cited by 211 · see citing works
The immunopathogenesis of fibrosis in systemic sclerosis
Brown, M., & O’Reilly, S. (2018) · Clinical & Experimental Immunology · doi:10.1111/cei.13238 · Cited by 192 · see citing works
New generation of mucosal adjuvants for the induction of protective immunity
Yuki, Y., & Kiyono, H. (2003) · Reviews in Medical Virology · doi:10.1002/rmv.398 · Cited by 192 · see citing works
Kedzierska, K., Crowe, S. M., Turville, S. G., & Cunningham, A. L. (2002) · Reviews in Medical Virology · doi:10.1002/rmv.369 · Cited by 192 · see citing works
- Authors
- Rincón, M., Anguita, J., Nakamura, T., Fikrig, E., & Flavell, R. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- From the *Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011; ‡Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-9031; and §Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1997-02-03
- Volume
- 185
- Issue
- 3
- Pages
- 461-470
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2196041
- OpenAlex
- W2150763544
- Cited by
- 810
- References
- 55
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 14 · 2023: 18 · 2022: 20 · 2021: 23 · 2020: 23 · 2019: 19 · 2018: 19 · 2017: 15 · 2016: 18 · 2015: 16 · 2014: 30 · 2013: 9 · 2012: 25
- FWCI
- 29.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ai030548-09)
- National Cancer Institute (CA-65861, R01CA065861)
- National Institute of Allergy and Infectious Diseases (1-P01-AI30548)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- interleukin-6, IL-4, CD4+ T cells, Th2 differentiation, Th1 differentiation, antigen-presenting cells, immune regulation
- MeSH terms
- Animals, Antigen-Presenting Cells, Cell Differentiation, Mice, Inbred C57BL, CD4-Positive T-Lymphocytes, Interleukin-4, Interleukin-6, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
