GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response
Abstract
Interleukin (IL)-10 and glucocorticoids (GCs) inhibit the ability of antigen-presenting dendritic cells (DCs) to stimulate T lymphocytes. We show that induction of GILZ (GC-induced leucine zipper) is involved in this phenomenon. IL-10, dexamethasone (DEX), and transforming growth factor (TGF)beta stimulate GILZ production in human immature DCs derived from monocytes and from CD34+ cells. GILZ is necessary and sufficient for DEX, IL-10, and TGFbeta modulation of CD80, CD83, CD86, immunoglobulin-like transcript (ILT)-3, and B7-H1 expression by DCs, and alteration of DC functions. GILZ stimulates the production of IL-10 by immature DCs and prevents the production of inflammatory chemokines by CD40L-activated DCs. In contrast, GILZ does not prevent CD40 ligand-mediated inhibition of phagocytosis, indicating that it affects some but not all aspects of DC maturation. GILZ prevents DCs from activating antigen-specific T lymphocyte responses. Administration of GCs to patients stimulates GILZ expression in their circulating antigen-presenting cells, and this contributes to the weak lymphocyte responses of GC-treated patients. Thus, regulation of GILZ expression is an important factor determining the decision of DCs whether or not to stimulate T lymphocytes, and IL-10, GCs, and TGFbeta share this mechanism for influencing DC functions and the balance between immune response and tolerance.
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Glucocorticoids can convert dendritic cells to tolerogenic cells that promote regulatory T cell production, and this effect relies on glucocorticoid-mediated expression of GILZ.
“GCs can also convert DCs to tolerogenic cells, which promote the production of regulatory T cells (38, 39). This immunosuppressive effect critically relies on the GC-mediated expression of glucocorticoid-induce leucine zipper (GILZ), since this transcription factor appears as both necessary and sufficient for the induction of a tolerogenic state (40, 41).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [40]
Cites
Interleukin-10 and the Interleukin-10 Receptor
Moore, K. W., de Waal Malefyt, R., Coffman, R. L., & O'Garra, A. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.683 · Cited by 6,737 · see citing works
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
Interleukin-10-deficient mice develop chronic enterocolitis
Kühn, R., Löhler, J., Rennick, D. M., Rajewsky, K., & Müller, W. (1993) · Cell · doi:10.1016/0092-8674(93)80068-p · Cited by 4,248 · see citing works
Steinman, R. M., Hawiger, D., & Nussenzweig, M. C. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141040 · Cited by 3,124 · see citing works
Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., Calvin, D., et al. (1992) · Nature · doi:10.1038/359693a0 · Cited by 2,985 · see citing works
Auphan, N., DiDonato, J. A., Rosette, C., Helmberg, A., & Karin, M. (1995) · Science · doi:10.1126/science.270.5234.286 · Cited by 2,390 · see citing works
Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo
Hawiger, D., Inaba, K., Dorsett, Y., Guo, M., Mahnke, K., Rivera, M. N., Ravetch, J. V., Steinman, R. M., & Nussenzweig, M. C. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.769 · Cited by 1,848 · see citing works
Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery
Zufferey, R., Dull, T., Mandel, R. J., Bukovsky, A., Quiroz, D., Naldini, L., & Trono, D. (1998) · Journal of Virology · doi:10.1128/jvi.72.12.9873-9880.1998 · Cited by 1,815 · see citing works
Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids
Scheinman, R. I., Cogswell, P. C., Lofquist, A. K., & Baldwin, A. S. (1995) · Science · doi:10.1126/science.270.5234.283 · Cited by 1,676 · see citing works
Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity
Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C., et al. (2003) · Nature Medicine · doi:10.1038/nm863 · Cited by 1,314 · see citing works
Co-inhibitory molecules of the B7–CD28 family in the control of T-cell immunity
Chen, L. (2004) · Nature reviews. Immunology · doi:10.1038/nri1349 · Cited by 1,257 · see citing works
Induction of tolerance by IL-10-treated dendritic cells
Steinbrink, K., Wölfl, M., Jonuleit, H., Knop, J., & Enk, A. H. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.10.4772 · Cited by 1,245 · see citing works
Expression of Programmed Death 1 Ligands by Murine T Cells and APC
Yamazaki, T., Akiba, H., Iwai, H., Matsuda, H., Aoki, M., Tanno, Y., Shin, T., Tsuchiya, H., Pardoll, D. M., Okumura, K., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5538 · Cited by 950 · see citing works
Regulatory T cells and mechanisms of immune system control
O’Garra, A., & Vieira, P. (2004) · Nature Medicine · doi:10.1038/nm0804-801 · Cited by 809 · see citing works
Latchman, Y. E., Liang, S. C., Wu, Y., Chernova, T., Sobel, R. A., Klemm, M., Kuchroo, V. K., Freeman, G. J., & Sharpe, A. H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307252101 · Cited by 631 · see citing works
Dendritic cells: emerging pharmacological targets of immunosuppressive drugs
Hackstein, H., & Thomson, A. W. (2004) · Nature reviews. Immunology · doi:10.1038/nri1256 · Cited by 546 · see citing works
Differentiation of T Regulatory Cells by Immature Dendritic Cells
Roncarolo, M., Levings, M. K., & Traversari, C. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.2.f5 · Cited by 484 · see citing works
D'Adamio, F., Zollo, O., Moraca, R., Ayroldi, E., Bruscoli, S., Bartoli, A., Cannarile, L., Migliorati, G., & Riccardi, C. (1997) · Immunity · doi:10.1016/s1074-7613(00)80398-2 · Cited by 444 · see citing works
TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells.
Geissmann, F., Revy, P., Régnault, A., Lepelletier, Y., Dy, M., Brousse, N., Amigorena, S., Hermine, O., & Durandy, A. (1999) · PubMed · Cited by 373 · see citing works
Brown, R. D., Pope, B., Murray, A., Esdale, W., Sze, D., Gibson, J., Ho, P. J., Hart, D. N. J., & Joshua, D. (2001) · Blood · doi:10.1182/blood.v98.10.2992 · Cited by 346 · see citing works
T cell costimulation by chemokine receptors
Molon, B., Gri, G., Bettella, M., Gómez‐Moutón, C., Lanzavecchia, A., Martínez‐A, C., Mañes, S., & Viola, A. (2005) · Nature Immunology · doi:10.1038/ni1191 · Cited by 343 · see citing works
Differentiation of human dendritic cells from monocytes in vitro
Chapuis, F., Rosenzwajg, M., Yagello, M., Ekman, M., Biberfeld, P., & Gluckman, J. C. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270213 · Cited by 338 · see citing works
TGF-β1 Prevents the Noncognate Maturation of Human Dendritic Langerhans Cells
Geissmann, F., Revy, P., Régnault, A., Lepelletier, Y., Dy, M., Brousse, N., Amigorena, S., Hermine, O., & Durandy, A. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.8.4567 · Cited by 333 · see citing works
Ayroldi, E., Migliorati, G., Bruscoli, S., Marchetti, C., Zollo, O., Cannarile, L., D'Adamio, F., & Riccardi, C. (2001) · Blood · doi:10.1182/blood.v98.3.743 · Cited by 318 · see citing works
Inhibition of AP-1 by the Glucocorticoid-inducible Protein GILZ
Mittelstadt, P. R., & Ashwell, J. D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101522200 · Cited by 301 · see citing works
Berrebi, D. D., Bruscoli, S., Cohen, N., Foussat, A., Migliorati, G., Bouchet‐Delbos, L., Maillot, M., Portier, A., Couderc, J., Galanaud, P., et al. (2002) · Blood · doi:10.1182/blood-2002-02-0538 · Cited by 290 · see citing works
Self-citationDiebold, R. J., Eis, M. J., Yin, M., Ormsby, I., Boivin, G. P., Darrow, B. J., Saffitz, J. E., & Doetschman, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.26.12215 · Cited by 278 · see citing works
Immune dysregulation in TGF- beta 1-deficient mice.
Christ, M., McCartney-Francis, N. L., Kulkarni, A. B., Ward, J. M., Mizel, D. E., Mackall, C. L., Gress, R. E., Hines, K. L., Tian, H., Karlsson, S., et al. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.5.1936 · Cited by 229 · see citing works
Autoimmune manifestations in the transforming growth factor-beta 1 knockout mouse
Yaswen, L. R., Kulkarni, A. B., Fredrickson, T. N., Mittleman, B. B., Schiffman, R. M., Payne, S., Longenecker, G., Mozes, E., & Karlsson, S. (1996) · Blood · doi:10.1182/blood.v87.4.1439.bloodjournal8741439 · Cited by 204 · see citing works
Réa, D., van Kooten, C., van Meijgaarden, K. E., Ottenhoff, T. H. M., Melief, C. J. M., & Offringa, R. (2000) · Blood · doi:10.1182/blood.v95.10.3162 · Cited by 184 · see citing works
Ayroldi, E., Zollo, O., Macchiarulo, A., Marco, B. D., Marchetti, C., & Riccardi, C. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.22.7929-7941.2002 · Cited by 182 · see citing works
Asselin-Labat, M.-L., David, M. D., Biola‐Vidamment, A., Lecoeuche, D., Zennaro, M., Bertoglio, J. H., & Pallardy, M. J. (2004) · Blood · doi:10.1182/blood-2003-12-4295 · Cited by 151 · see citing works
Self-citationZou, W., Borvak, J., Marches, F., Wei, S., Galanaud, P., Émilie, D., & Curiel, T. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.8.4388 · Cited by 137 · see citing works
Self-citationDupuy, F., Mouly, E., Mesel-Lemoine, M., Morel, C., Abriol, J., Cheraı, M., Baillou, C., Nègre, D., Cosset, F., Klatzmann, D., et al. (2005) · Journal of Gene Medicine · doi:10.1002/jgm.769 · Cited by 51 · see citing works
Self-citationGroux, H., Sornasse, T., Cottrez, F., de Vries, J. E., Coffman, R., Roncarolo, M., & Yssel, H. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.12.5627 · Cited by 48 · see citing works
Groux, H., Sornasse, T., Cottrez, F., de Vries, J. E., Coffman, R. L., Roncarolo, M., & Yssel, H. (1997) · PubMed · Cited by 47 · see citing works
Movassagh, M., Baillou, C., Cosset, F., et al. (1999) · Human Gene Therapy · doi:10.1089/10430349950018977 · Cited by 42 · see citing works
Rimaniol, A., Garcia, G., Till, S. J., et al. (2003) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2003.02118.x · Cited by 23 · see citing works
Lemoine, F. M., Mesel-Lemoine, M., Cheraı, M., Gallot, G., Vié, H., Leclercq, V., Trebeden-Negre, H., Mammès, O., Boyer, O., Noguiez-Hellin, P., et al. (2004) · Journal of Gene Medicine · doi:10.1002/jgm.538 · Cited by 19 · see citing works
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Coutinho, A. E., & Chapman, K. E. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.04.005 · Cited by 1,815 · see citing works
The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain
Bellavance, M.-A., & Rivest, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00136 · Cited by 419 · see citing works
Beck, I. M. E., Vanden Berghe, W., Vermeulen, L., Yamamoto, K. R., Haegeman, G., & De Bosscher, K. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0013 · Cited by 298 · see citing works
Hamdi, H., Godot, V., Maillot, M.-C., Prejean, M. V., Cohen, N., Krzysiek, R., Lemoine, F. M., Zou, W., & Emilie, D. (2007) · Blood · doi:10.1182/blood-2006-10-052506 · Cited by 126 · see citing works
Self-citationHontelez, S., Karthaus, N., Looman, M. W., Ansems, M., & Adema, G. J. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201776 · Cited by 35 · see citing works
- Authors
- Cohen, N., Mouly, E., Hamdi, H., Maillot, M.-C., Pallardy, M., Godot, V., Capel, F., Balian, A., Naveau, S., Galanaud, P., Lemoine, F. M., & Emilie, D.
- Affiliations
- Université Paris-Sud (FR)
- From the INSERM UMR-S764, Service d'Hépato-Gastro-Entérologie and Service de Microbiologie—Immunologie Biologique, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, Institut Paris-Sud sur les Cytokines, Université Paris-Sud, Clamart, France; CNRS UMR 7087/UPMC, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, France; and INSERM UMR-S749, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-03-01
- Volume
- 107
- Issue
- 5
- Pages
- 2037-2044
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2132254923
- Cited by
- 170
- References
- 39
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 6 · 2017: 13 · 2016: 6 · 2015: 16 · 2014: 13 · 2013: 8 · 2012: 12
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- GILZ, dendritic cell maturation, dendritic cells, T cell activation, IL-10, glucocorticoids, dexamethasone, TGF-beta, CD80, CD83, CD86, PD-L1, CD40 ligand, antigen presentation, immune tolerance, chemokine production, monocyte-derived dendritic cells, CD34+ cells
- MeSH terms
- Anti-Inflammatory Agents, Cell Differentiation, Cells, Cultured, Dendritic Cells, Gene Expression Regulation, Humans, Immune Tolerance, Lymphocyte Activation, T-Lymphocytes, Transcription Factors, Antigens, CD, Cytokines
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