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GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus

Glucocorticoid-induced leucine zipper (GILZ) mimics many of the anti-inflammatory effects of glucocorticoids, suggesting it as a point of therapeutic intervention that could bypass GC adverse effects. We previously reported that GILZ down-regulation is a feature of human SLE, and loss of GILZ permit...

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Autores principales: Nataraja, Champa, Dankers, Wendy, Flynn, Jacqueline, Lee, Jacinta P. W., Zhu, Wendy, Vincent, Fabien B., Gearing, Linden J., Ooi, Joshua, Pervin, Mehnaz, Cristofaro, Megan A., Sherlock, Rochelle, Hasnat, Md Abul, Harris, James, Morand, Eric F., Jones, Sarah A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056982/
https://www.ncbi.nlm.nih.gov/pubmed/33889157
http://dx.doi.org/10.3389/fimmu.2021.652800
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author Nataraja, Champa
Dankers, Wendy
Flynn, Jacqueline
Lee, Jacinta P. W.
Zhu, Wendy
Vincent, Fabien B.
Gearing, Linden J.
Ooi, Joshua
Pervin, Mehnaz
Cristofaro, Megan A.
Sherlock, Rochelle
Hasnat, Md Abul
Harris, James
Morand, Eric F.
Jones, Sarah A.
author_facet Nataraja, Champa
Dankers, Wendy
Flynn, Jacqueline
Lee, Jacinta P. W.
Zhu, Wendy
Vincent, Fabien B.
Gearing, Linden J.
Ooi, Joshua
Pervin, Mehnaz
Cristofaro, Megan A.
Sherlock, Rochelle
Hasnat, Md Abul
Harris, James
Morand, Eric F.
Jones, Sarah A.
author_sort Nataraja, Champa
collection PubMed
description Glucocorticoid-induced leucine zipper (GILZ) mimics many of the anti-inflammatory effects of glucocorticoids, suggesting it as a point of therapeutic intervention that could bypass GC adverse effects. We previously reported that GILZ down-regulation is a feature of human SLE, and loss of GILZ permits the development of autoantibodies and lupus-like autoimmunity in mice. To further query the contribution of GILZ to protection against autoimmune inflammation, we studied the development of the lupus phenotype in Lyn-deficient (Lyn(-/-)) mice in which GILZ expression was genetically ablated. In Lyn(-/-) mice, splenomegaly, glomerulonephritis, anti-dsDNA antibody titres and cytokine expression were exacerbated by GILZ deficiency, while other autoantibody titres and glomerular immune complex deposition were unaffected. Likewise, in patients with SLE, GILZ was inversely correlated with IL23A, and in SLE patients not taking glucocorticoids, GILZ was also inversely correlated with BAFF and IL18. This suggests that at the onset of autoimmunity, GILZ protects against tissue injury by modulating pro-inflammatory pathways, downstream of antibodies, to regulate the cycle of inflammation in SLE.
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spelling pubmed-80569822021-04-21 GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus Nataraja, Champa Dankers, Wendy Flynn, Jacqueline Lee, Jacinta P. W. Zhu, Wendy Vincent, Fabien B. Gearing, Linden J. Ooi, Joshua Pervin, Mehnaz Cristofaro, Megan A. Sherlock, Rochelle Hasnat, Md Abul Harris, James Morand, Eric F. Jones, Sarah A. Front Immunol Immunology Glucocorticoid-induced leucine zipper (GILZ) mimics many of the anti-inflammatory effects of glucocorticoids, suggesting it as a point of therapeutic intervention that could bypass GC adverse effects. We previously reported that GILZ down-regulation is a feature of human SLE, and loss of GILZ permits the development of autoantibodies and lupus-like autoimmunity in mice. To further query the contribution of GILZ to protection against autoimmune inflammation, we studied the development of the lupus phenotype in Lyn-deficient (Lyn(-/-)) mice in which GILZ expression was genetically ablated. In Lyn(-/-) mice, splenomegaly, glomerulonephritis, anti-dsDNA antibody titres and cytokine expression were exacerbated by GILZ deficiency, while other autoantibody titres and glomerular immune complex deposition were unaffected. Likewise, in patients with SLE, GILZ was inversely correlated with IL23A, and in SLE patients not taking glucocorticoids, GILZ was also inversely correlated with BAFF and IL18. This suggests that at the onset of autoimmunity, GILZ protects against tissue injury by modulating pro-inflammatory pathways, downstream of antibodies, to regulate the cycle of inflammation in SLE. Frontiers Media S.A. 2021-04-06 /pmc/articles/PMC8056982/ /pubmed/33889157 http://dx.doi.org/10.3389/fimmu.2021.652800 Text en Copyright © 2021 Nataraja, Dankers, Flynn, Lee, Zhu, Vincent, Gearing, Ooi, Pervin, Cristofaro, Sherlock, Hasnat, Harris, Morand and Jones https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Nataraja, Champa
Dankers, Wendy
Flynn, Jacqueline
Lee, Jacinta P. W.
Zhu, Wendy
Vincent, Fabien B.
Gearing, Linden J.
Ooi, Joshua
Pervin, Mehnaz
Cristofaro, Megan A.
Sherlock, Rochelle
Hasnat, Md Abul
Harris, James
Morand, Eric F.
Jones, Sarah A.
GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus
title GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus
title_full GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus
title_fullStr GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus
title_full_unstemmed GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus
title_short GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus
title_sort gilz regulates the expression of pro-inflammatory cytokines and protects against end-organ damage in a model of lupus
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056982/
https://www.ncbi.nlm.nih.gov/pubmed/33889157
http://dx.doi.org/10.3389/fimmu.2021.652800
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