Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice
Glucocorticoid-induced leucine zipper (GILZ) is transcriptionally upregulated by glucocorticoids (GCs) and mediates many of the anti-inflammatory effects of GCs. Since B cell activity has been linked to cytokine production and modulation of inflammatory responses, we herein investigated the role of...
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01720/full |
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| author | Stefano Bruscoli Daniele Sorcini Sara Flamini Andrea Gagliardi Francesco Adamo Simona Ronchetti Graziella Migliorati Oxana Bereshchenko Carlo Riccardi |
| author_facet | Stefano Bruscoli Daniele Sorcini Sara Flamini Andrea Gagliardi Francesco Adamo Simona Ronchetti Graziella Migliorati Oxana Bereshchenko Carlo Riccardi |
| author_sort | Stefano Bruscoli |
| collection | DOAJ |
| description | Glucocorticoid-induced leucine zipper (GILZ) is transcriptionally upregulated by glucocorticoids (GCs) and mediates many of the anti-inflammatory effects of GCs. Since B cell activity has been linked to cytokine production and modulation of inflammatory responses, we herein investigated the role of GILZ in B cells during colitis development. B cell-specific gilz knock-out (gilz B cKO) mice exhibited increased production of the pro-inflammatory cytokine IFN-γ in B cells, and consequently CD4+ T cell activation. Increased IFN-γ production in B cells was associated with enhanced transcriptional activity of the transcription factor activator protein-1 (AP-1) on the IFN-γ promoter. Moreover, GILZ deficiency in B cells was linked to enhanced susceptibility to experimental colitis in mice, and this was reversed by administering GILZ protein. Interestingly, we observed increased production of IFN-γ in both B and T cells infiltrating the lamina propria (LP) of gilz B cKO mice. Together, these findings indicate that GILZ controls IFN-γ production in B cells, which also affects T cell activity, and increased production of IFN-γ by B and T cells in LP is associated with predisposition to inflammatory colitis in mice. |
| first_indexed | 2024-12-10T16:49:57Z |
| format | Article |
| id | doaj.art-ff33e2cca2544a7fb14b3178c2335548 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T16:49:57Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ff33e2cca2544a7fb14b3178c23355482022-12-22T01:40:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01720383855Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in MiceStefano Bruscoli0Daniele Sorcini1Sara Flamini2Andrea Gagliardi3Francesco Adamo4Simona Ronchetti5Graziella Migliorati6Oxana Bereshchenko7Carlo Riccardi8Section of Pharmacology, Department of Medicine, University of Perugia, Perugia, ItalySection of Hematology, Department of Medicine, University of Perugia, Perugia, ItalySection of Pharmacology, Department of Medicine, University of Perugia, Perugia, ItalySection of Pharmacology, Department of Medicine, University of Perugia, Perugia, ItalySection of Pharmacology, Department of Medicine, University of Perugia, Perugia, ItalySection of Pharmacology, Department of Medicine, University of Perugia, Perugia, ItalySection of Pharmacology, Department of Medicine, University of Perugia, Perugia, ItalyDepartment of Surgery and Biomedical Sciences, University of Perugia, Perugia, ItalySection of Pharmacology, Department of Medicine, University of Perugia, Perugia, ItalyGlucocorticoid-induced leucine zipper (GILZ) is transcriptionally upregulated by glucocorticoids (GCs) and mediates many of the anti-inflammatory effects of GCs. Since B cell activity has been linked to cytokine production and modulation of inflammatory responses, we herein investigated the role of GILZ in B cells during colitis development. B cell-specific gilz knock-out (gilz B cKO) mice exhibited increased production of the pro-inflammatory cytokine IFN-γ in B cells, and consequently CD4+ T cell activation. Increased IFN-γ production in B cells was associated with enhanced transcriptional activity of the transcription factor activator protein-1 (AP-1) on the IFN-γ promoter. Moreover, GILZ deficiency in B cells was linked to enhanced susceptibility to experimental colitis in mice, and this was reversed by administering GILZ protein. Interestingly, we observed increased production of IFN-γ in both B and T cells infiltrating the lamina propria (LP) of gilz B cKO mice. Together, these findings indicate that GILZ controls IFN-γ production in B cells, which also affects T cell activity, and increased production of IFN-γ by B and T cells in LP is associated with predisposition to inflammatory colitis in mice.https://www.frontiersin.org/article/10.3389/fimmu.2018.01720/fullcorticosteroidglucocorticoid-induced leucine zipperinflammationIFN-γmouse models |
| spellingShingle | Stefano Bruscoli Daniele Sorcini Sara Flamini Andrea Gagliardi Francesco Adamo Simona Ronchetti Graziella Migliorati Oxana Bereshchenko Carlo Riccardi Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice Frontiers in Immunology corticosteroid glucocorticoid-induced leucine zipper inflammation IFN-γ mouse models |
| title | Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice |
| title_full | Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice |
| title_fullStr | Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice |
| title_full_unstemmed | Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice |
| title_short | Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice |
| title_sort | glucocorticoid induced leucine zipper inhibits interferon gamma production in b cells and suppresses colitis in mice |
| topic | corticosteroid glucocorticoid-induced leucine zipper inflammation IFN-γ mouse models |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01720/full |
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