Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper
Abstract
Dendritic cells (DCs) determine whether antigen presentation leads to immune activation or to tolerance. Tolerance-inducing DCs (also called regulatory DCs) act partly by generating regulatory T lymphocytes (Tregs). The mechanism used by DCs to switch toward regulatory DCs during their differentiation is unclear. We show here that human DCs treated in vitro with glucocorticoids produce the glucocorticoid-induced leucine zipper (GILZ). Antigen presentation by GILZ-expressing DCs generates CD25highFOXP3+CTLA-4/CD152+ and interleukin-10–producing Tregs inhibiting the response of CD4+ and CD8+ T lymphocytes. This inhibition is specific to the antigen presented, and only proliferating CD4+ T lymphocytes express the Treg markers. Interleukin-10 is required for Treg induction by GILZ-expressing DCs. It is also needed for the suppressive function of Tregs. Antigen-presenting cells from patients treated with glucocorticoids generate interleukin-10–secreting Tregs ex vivo. These antigen-presenting cells produce GILZ, which is needed for Treg induction. Therefore, GILZ is critical for commitment of DCs to differentiate into regulatory DCs and to the generation of antigen-specific Tregs. This mechanism may contribute to the therapeutic effects of glucocorticoids.
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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 [41]
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- Authors
- Hamdi, H., Godot, V., Maillot, M.-C., Prejean, M. V., Cohen, N., Krzysiek, R., Lemoine, F. M., Zou, W., & Emilie, D.
- Affiliations
- Institut National de la Santé et de la Recherche Médicale, U764, Clamart, France;
- Université Paris-Sud (FR)
- Inserm (FR)
- Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7087, Paris, France;
- University of Michigan (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-07-01
- Volume
- 110
- Issue
- 1
- Pages
- 211-219
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2025019393
- Cited by
- 126
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 13 · 2014: 12 · 2013: 8 · 2012: 6
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- National Heart, Lung, and Blood Institute (R01HL079584, R01HL074399, R01HL080499)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- regulatory T cells, dendritic cells, GILZ, glucocorticoids, regulatory dendritic cells, antigen-specific tolerance, IL-10, Foxp3, CTLA-4, CD25, Treg induction, immune tolerance, CD4+ T cells, CD8+ T cells, glucocorticoid therapy
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