IL‐6 promotes immune responses in human ulcerative colitis and induces a skin‐homing phenotype in the dendritic cells and T cells they stimulate
Open accessAbstract
Dendritic cells (DC s) control the type and location of immune responses. Ulcerative colitis (UC) is considered a T h2 disease mediated by IL‐13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DC s from healthy controls. Levels of IL‐13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a T h2 cytokine profile. IL‐6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the M ayo endoscopic score for severity of disease. DC s conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DC s conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin‐homing chemokine CCR 8. These DC s did not have decreased T‐cell stimulatory capacity and primed T cells with the skin‐homing CLA molecule in an IL‐6‐dependent mechanism. Our results highlight the role of IL‐6 in UC and question the concept of UC as a T h2 disease and the relevance of IL‐13 in its etiology.
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In this patient, IL-6, TNF-α and IL-17A were elevated during rejection phase and were likely promoting observed skin and gastrointestinal toxicities.
“In this patient, several other inflammatory cytokines, mainly IL-6, TNF-α and IL-17A, were also elevated during the rejection phase, and were likely promoting the observed concomitant skin and gastrointestinal toxicities29–31.”
From Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation (2019) · cites this paper as [29]
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Cites
Dendritic cells and the control of immunity
Banchereau, J., & Steinman, R. M. (1998) · Nature · doi:10.1038/32588 · Cited by 14,244 · see citing works
Coombes, J. L., Siddiqui, K. R. R., Arancibia-Cárcamo, C. V., Hall, J. A., Sun, C., Belkaid, Y., & Powrie, F. M. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070590 · Cited by 2,708 · see citing works
Vitamin effects on the immune system: Vitamins A and D take centre stage
Mora, J. R., Iwata, M., & von Andrian, U. H. (2008) · Nature Reviews Immunology · doi:10.1038/nri2378 · Cited by 1,559 · see citing works
Retinoic acid imprints gut-homing specificity on T cells
Iwata, M., Hirakiyama, A., Eshima, Y., Kagechika, H., Kato, C., & Song, S.-Y. (2004) · Immunity · doi:10.1016/j.immuni.2004.08.011 · Cited by 1,541 · see citing works
Anatomical basis of tolerance and immunity to intestinal antigens
Mowat, A. M. (2003) · Nature reviews. Immunology · doi:10.1038/nri1057 · Cited by 1,414 · see citing works
Heller, F., Florian, P., Bojarski, C., Richter, J. F., Christ, M., Hillenbrand, B., Mankertz, J., Gitter, A. H., Bürgel, N., Fromm, M., et al. (2005) · Gastroenterology · doi:10.1016/j.gastro.2005.05.002 · Cited by 1,237 · see citing works
Proinflammatory Cytokines in the Pathogenesis of Inflammatory Bowel Diseases
Strober, W., & Fuss, I. J. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.016 · Cited by 1,105 · see citing works
Heller, F., Florian, P., Bojarski, C., et al. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.05.002 · Cited by 1,016 · see citing works
Generation of Gut-Homing IgA-Secreting B Cells by Intestinal Dendritic Cells
Mora, J. R., Iwata, M., Eksteen, B., Song, S., Junt, T., Senman, B. C., Otipoby, K. L., Yokota, A., Takeuchi, H., Ricciardi‐Castagnoli, P., et al. (2006) · Science · doi:10.1126/science.1132742 · Cited by 1,014 · see citing works
Hadis, U., Wahl, B., Schulz, O., Hardtke-Wolenski, M., Schippers, A., Wagner, N., Müller, W., Sparwasser, T., Förster, R., & Pabst, O. (2011) · Immunity · doi:10.1016/j.immuni.2011.01.016 · Cited by 893 · see citing works
Origin of the Lamina Propria Dendritic Cell Network
Bogunovic, M., Ginhoux, F., Helft, J., Shang, L., Hashimoto, D., Greter, M., Liu, K., Jakubzick, C., Ingersoll, M. A., Leboeuf, M., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.010 · Cited by 859 · see citing works
Rimoldi, M., Chieppa, M., Salucci, V., Avogadri, F., Sonzogni, A., Sampietro, G. M., Nespoli, A., Viale, G., Allavena, P., & Rescigno, M. (2005) · Nature Immunology · doi:10.1038/ni1192 · Cited by 815 · see citing works
Intestinal Lamina Propria Dendritic Cell Subsets Have Different Origin and Functions
Varol, C., Vallon-Eberhard, A., Elinav, E., Aychek, T., Shapira, Y., Luche, H., Fehling, H. J., Hardt, W., Shakhar, G., & Jung, S. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.025 · Cited by 710 · see citing works
Schulz, O., Gyllenbäck, E. J., Persson, E. K., Liu, X., Worbs, T., Agace, W. W., & Pabst, O. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20091925 · Cited by 702 · see citing works
Role of cytokines in inflammatory bowel disease
Sanchez-Muñoz, F., Dominguez-Lopez, A., & Yamamoto-Furusho, J. K. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.4280 · Cited by 699 · see citing works
Characteristics of Intestinal Dendritic Cells in Inflammatory Bowel Diseases
Hart, A. L., Al-Hassi, H. O., Rigby, R. J., Bell, S., Emmanuel, A. V., Knight, S. C., Kamm, M. A., & Stagg, A. J. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.05.013 · Cited by 562 · see citing works
Self-citationRivollier, A., He, J., Kole, A., Valatas, V., & Kelsall, B. L. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20101387 · Cited by 548 · see citing works
Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens
DePaolo, R. W., Abadie, V., Tang, F., Fehlner-Peach, H., Hall, J. A., Wang, W., Marietta, E. V., Kasarda, D. D., Waldmann, T. A., Murray, J. A., et al. (2011) · Nature · doi:10.1038/nature09849 · Cited by 392 · see citing works
Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells
Iliev, I. D., Spadoni, I., Mileti, E., Matteoli, G., Sonzogni, A., Sampietro, G. M., Foschi, D., Caprioli, F., Viale, G., & Rescigno, M. (2009) · Gut · doi:10.1136/gut.2008.175166 · Cited by 389 · see citing works
Iliev, I. D., Mileti, E., Matteoli, G., Chieppa, M., & Rescigno, M. (2009) · Mucosal Immunology · doi:10.1038/mi.2009.13 · Cited by 354 · see citing works
Li, Y., de Haar, C., Chen, M., Deuring, J., Gerrits, M. M., Smits, R., Xia, B., Kuipers, E. J., & van der Woude, C. J. (2010) · Gut · doi:10.1136/gut.2009.184176 · Cited by 339 · see citing works
Environmental cues, dendritic cells and the programming of tissue-selective lymphocyte trafficking
Sigmundsdóttir, H., & Butcher, E. C. (2008) · Nature Immunology · doi:10.1038/ni.f.208 · Cited by 330 · see citing works
Larsen, S., Bendtzen, K., & Nielsen, O. H. (2010) · Annals of Medicine · doi:10.3109/07853890903559724 · Cited by 298 · see citing works
Lundgren, A., Strömberg, E., Sjöling, Å., Lindholm, C., Enarsson, K., Edebo, A., Johnsson, E., Suri‐Payer, E., Larsson, P., Rudin, A., et al. (2004) · Infection and Immunity · doi:10.1128/iai.73.1.523-531.2005 · Cited by 268 · see citing works
Immunomodulatory dendritic cells in intestinal lamina propria
Chirdo, F. G., Millington, O. R., Beacock‐Sharp, H., & Mowat, A. M. (2005) · European Journal of Immunology · doi:10.1002/eji.200425882 · Cited by 229 · see citing works
CD4+CD25+ Tregs and NKT cells: regulators regulating regulators
Cava, A. L., Kaer, L. V., & Fu-Dong-Shi (2006) · Trends in Immunology · doi:10.1016/j.it.2006.05.003 · Cited by 208 · see citing works
Intestinal inflammation abrogates the tolerogenic properties of MLN CD103 + dendritic cells
Laffont, S., Siddiqui, K. R. R., & Powrie, F. M. (2010) · European Journal of Immunology · doi:10.1002/eji.200939957 · Cited by 193 · see citing works
Humanized Antihuman IL-6 Receptor Antibody, Tocilizumab
Nishimoto, N., & Kishimoto, T. (2007) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-73259-4_7 · Cited by 185 · see citing works
Role of retinoic acid in the imprinting of gut-homing IgA-secreting cells
Mora, J. R., & von Andrian, U. H. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2008.08.002 · Cited by 174 · see citing works
Mouse and human intestinal immunity: same ballpark, different players; different rules, same score
Gibbons, D. L., & Spencer, J. (2011) · Mucosal Immunology · doi:10.1038/mi.2010.85 · Cited by 170 · see citing works
Dudda, J. C., Lembo, A., Bachtanian, E., Huehn, J., Siewert, C., Hamann, A., Kremmer, E., Förster, R., & Martin, S. F. (2005) · European Journal of Immunology · doi:10.1002/eji.200425817 · Cited by 168 · see citing works
Stunz, L. L., Lenert, P. S., Peckham, D., Yi, A., Haxhinasto, S. A., Chang, M., Krieg, A. Μ., & Ashman, R. F. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200205)32:5 · Cited by 150 · see citing works
Arihiro, S., Ohtani, H., Suzuki, M., Murata, M., Ejima, C., Oki, M., Kinouchi, Y., Fukushima, K., Sasaki, I., Nakamura, S., et al. (2002) · Pathology International · doi:10.1046/j.1440-1827.2002.01365.x · Cited by 143 · see citing works
Olsen, T., Rismo, R., Cui, G., Goll, R., Christiansen, I., & Florholmen, J. (2011) · Cytokine · doi:10.1016/j.cyto.2011.08.036 · Cited by 136 · see citing works
Inoue, S., Matsumoto, T., Iida, M., Mizuno, M., Kuroki, F., Hoshika, K., & Shimizu, M. (1999) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1999.01372.x · Cited by 129 · see citing works
Veloso, F. T. (2011) · World Journal of Gastroenterology · doi:10.3748/wjg.v17.i22.2702 · Cited by 129 · see citing works
Functionally distinct NKT cell subsets and subtypes
Seino, K., & Taniguchi, M. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051600 · Cited by 122 · see citing works
Leon, A. J., Gómez, E., Garrote, J. A., Bernardo, D., Barrera, A., Marcos, J. L., Fernández-Salazar, L. I., Velayos, B., Blanco-Quirós, A., & Arranz, E. M. (2009) · Mediators of Inflammation · doi:10.1155/2009/580450 · Cited by 118 · see citing works
Self-citationOral tolerance: is it all retinoic acid?
von Boehmer, H. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20071251 · Cited by 97 · see citing works
Kawashima, R., Kawamura, Y. I., Oshio, T., Son, A., Yamazaki, M., Hagiwara, T., Okada, T., Inagaki-Ohara, K., Wu, P., Szak, S. T., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.08.040 · Cited by 82 · see citing works
Hyperlog—A flexible log‐like transform for negative, zero, and positive valued data
Bagwell, C. B. (2005) · Cytometry Part A · doi:10.1002/cyto.a.20114 · Cited by 80 · see citing works
Mitsuyama, K., Matsumoto, S., Masuda, J., Yamasakii, H., Kuwaki, K., Takedatsu, H., & Sata, M. (2007) · PubMed · Cited by 75 · see citing works
Modulation of dendritic cell phenotype and functionin an in vitro model of the intestinal epithelium
Butler, M., Ng, C., van Heel, D. A., Lombardi, G., Lechler, R. I., Playford, R. J., & Ghosh, S. K. (2006) · European Journal of Immunology · doi:10.1002/eji.200535497 · Cited by 75 · see citing works
Dendritic cells: the commanders-in-chief of mucosal immune defenses
Niess, J. H., & Reinecker, H. (2006) · Current Opinion in Gastroenterology · doi:10.1097/01.mog.0000231807.03149.54 · Cited by 72 · see citing works
Higher constitutive IL15Rα expression and lower IL-15 response threshold in coeliac disease patients
Bernardo, D., Garrote, J. A., Allegretti, Y., et al. (2008) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2008.03743.x · Cited by 72 · see citing works
Self-citationImpaired Retinoic Acid (RA) Signal Leads to RARβ2 Epigenetic Silencing and RA Resistance
Ren, M., Pozzi, S., Bistulfi, G. L., Somenzi, G., Rossetti, S., & Sacchi, N. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.23.10591-10603.2005 · Cited by 60 · see citing works
Kim, H. J., Hwang, S. J., Kim, B. K., et al. (2006) · Immunology · doi:10.1111/j.1365-2567.2006.02346.x · Cited by 55 · see citing works
Ozbek, S. M., Özbek, A., & Erdorgan, A. S. (2009) · Journal of Applied Oral Science · doi:10.1590/s1678-77572009000500004 · Cited by 43 · see citing works
Pivotal roles of interleukin-6 in transmural inflammation in murine T cell transfer colitis
Kitamura, K., Nakamoto, Y., Kaneko, S., & Mukaida, N. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0604328 · Cited by 34 · see citing works
Hart, A. L., Kamm, M. A., Knight, S. C., & Stagg, A. J. (2003) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2004.02347.x · Cited by 28 · see citing works
Self-citationNg, S. C., Plamondon, S., Al-Hassi, H. O., et al. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2009.04012.x · Cited by 28 · see citing works
Self-citationDecreased circulating iNKT cell numbers in refractory coeliac disease
Bernardo, D., van Hoogstraten, I. M. W., Verbeek, W. H. M., Peña, A. S., Mearin, M. L., Arranz, E. M., Garrote, J. A., Scheper, R. J., Schreurs, M. W. J., Bontkes, H. J., et al. (2007) · Clinical Immunology · doi:10.1016/j.clim.2007.09.005 · Cited by 24 · see citing works
Self-citationProspective Evaluation of Intestinal Homing Memory T Cells in Ulcerative Colitis
Hart, A. L., Kamm, M. A., Knight, S. C., et al. (2004) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200409000-00002 · Cited by 16 · see citing works
Self-citationHuff, K. R., Akhtar, L. N., Fox, A. L., Cannon, J. A., Smith, P. D., & Smythies, L. E. (2011) · Mucosal Immunology · doi:10.1038/mi.2010.86 · Cited by 16 · see citing works
Holden, N. J., Bedford, P., McCarthy, N. E., et al. (2008) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2008.02997.x · Cited by 15 · see citing works
Solari, N. E. F., Galoppo, C., Cuarterolo, M. L., et al. (2010) · Clinical Immunology · doi:10.1016/j.clim.2010.08.013 · Cited by 13 · see citing works
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- Mann, E. R., Bernardo, D., Al-Hassi, H. O., English, N. R., Clark, S. K., McCarthy, N. E., Milestone, A. N., et al. In humans, gut-specific home- ostatic dendritic cells are generated from blood precursors by the gut microenvironment. Inflamm. Bowel Dis. 2011. In press.
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Esfahani, K., Al-Aubodah, T.-A., Thebault, P., Lapointe, R., Hudson, M., Johnson, N. A., Baran, D., Bhulaiga, N., Takano, T., Cailhier, J.-F., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12628-1 · Cited by 109 · see citing works
- Authors
- Bernardo, D., Vallejo‐Díez, S., Mann, E. R., Al‐Hassi, H. O., Martínez‐Abad, B., Montalvillo, E., Tee, C. T., Murugananthan, A. U., Núñez, H., Peake, S. T. C., Hart, A. L., Fernández‐Salazar, L., Garrote, J. A., Arranz, E., & Knight, S. C.
- Affiliations
- Imperial College London (GB)
- Universidad de Valladolid (ES)
- Antigen Presentation Research Group, Imperial College London Northwick Park & St Mark's Campus Watford Road Harrow United Kingdom
- Hospital Universitario Río Hortega (ES)
- London North West Healthcare NHS Trust (GB)
- Gastroenterology Service Hospital Clínico Universitario de Valladolid Valladolid Spain
- Genetics and Molecular Biology Lab, Service of Clinical Laboratory Hospital Universitario Río Hortega Valladolid Spain
- Corresponding author
- Knight, Stella C.
- ORCID
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2012-04-26
- Volume
- 42
- Issue
- 5
- Pages
- 1337-1353
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W1533566241
- Cited by
- 77
- References
- 57
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 8 · 2013: 5
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Marie Curie Intra European Fellowship (FP7-people-IEF-2008-235993)
- St Mark's Hospital Foundation
- Brigid Balfour Fund
- Junta de Castilla y León (GRS175/B/07)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- ulcerative colitis, interleukin-6, dendritic cells, skin-homing T cells, CCR8, CLA, IL-13, extraintestinal manifestations, disease severity, T cell priming, regulatory dendritic cells, chemokines
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cells, Cultured, Colitis, Ulcerative, Dendritic Cells, Female, Humans, Inflammation, Male, Middle Aged, Severity of Illness Index, Skin, T-Lymphocytes, Interleukin-6, Cytokines, Th2 Cells, Interleukin-13
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