image_4_Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice.jpeg
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.
History
References
- https://doi.org//10.1016/j.rdc.2015.08.002
- https://doi.org//10.1006/phrs.2002.0969
- https://doi.org//10.1038/sj.cdd.4400798
- https://doi.org//10.1016/S1074-7613(00)80398-2
- https://doi.org//10.4049/jimmunol.1302338
- https://doi.org//10.1182/blood-2002-02-0538
- https://doi.org//10.4049/jimmunol.1403207
- https://doi.org//10.1007/978-1-4615-0685-0_5
- https://doi.org//10.4049/jimmunol.1401722
- https://doi.org//10.1093/nar/gkl1080
- https://doi.org//10.1136/ard.2010.140533
- https://doi.org//10.1074/jbc.M101522200
- https://doi.org//10.1182/blood-2003-12-4295
- https://doi.org//10.1182/blood.V98.3.743
- https://doi.org//10.1182/blood-2005-05-2183
- https://doi.org//10.1007/s13311-011-0084-7
- https://doi.org//10.1053/j.gastro.2008.09.024
- https://doi.org//10.1016/S0016-5085(98)70381-6
- https://doi.org//10.1084/jem.20011956
- https://doi.org//10.1146/annurev.immunol.24.021605.090517
- https://doi.org//10.1038/nrneph.2014.80
- https://doi.org//10.1016/j.immuni.2015.04.005
- https://doi.org//10.1038/ni.2569
- https://doi.org//10.4049/jimmunol.174.11.6781
- https://doi.org//10.4049/jimmunol.175.11.7103
- https://doi.org//10.1038/82717
- https://doi.org//10.1016/S1074-7613(04)00112-8
- https://doi.org//10.1182/blood-2015-03-631580
- https://doi.org//10.1074/jbc.M111.316372
- https://doi.org//10.1093/nar/25.6.1317
- https://doi.org//10.1016/j.celrep.2014.03.004
- https://doi.org//10.1084/jem.189.1.1
- https://doi.org//10.1146/annurev.immunol.15.1.749
- https://doi.org//10.1084/jem.20100052
- https://doi.org//10.1038/cr.2013.155
- https://doi.org//10.4049/jimmunol.169.12.6664
- https://doi.org//10.1084/jem.178.1.237
- https://doi.org//10.1016/1074-7613(95)90086-1
- https://doi.org//10.1084/jem.186.10.1749
- https://doi.org//10.4049/jimmunol.1103354
- https://doi.org//10.1038/ni833
- https://doi.org//10.1093/intimm/12.5.597
- https://doi.org//10.1097/01.MIB.0000437983.14544.d5
- https://doi.org//10.1016/j.immuni.2009.01.006
- https://doi.org//10.1016/j.immuni.2008.03.017
- https://doi.org//10.4049/jimmunol.1001431
- https://doi.org//10.4049/jimmunol.169.8.4205
- https://doi.org//10.1002/emmm.201201683
- https://doi.org//10.1046/j.1365-2249.1996.48757.x
Usage metrics
Read the peer-reviewed publication
Categories
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity