Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells

Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive agents. Several studies have indicated the important role of dendritic cells (DCs), highly specialized antigen-presenting and immunomodulatory cells, in GC-mediated suppression of adaptive immune responses. Recently, we...

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Autores principales:	Montesinos, M.M., Alamino, V.A., Mascanfroni, I.D., Susperreguy, S., Gigena, N., Masini-Repiso, A.M., Rabinovich, G.A., Pellizas, C.G.
Formato:	JOUR
Materias:	Dendritic cells Dexamethasone Thyroid hormone action dexamethasone glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 10 interleukin 12 liothyronine protein kinase B animal cell antiinflammatory activity article cell maturation controlled study cytokine production cytokine release dendritic cell drug effect drug mechanism female lymphocyte proliferation mouse nonhuman Th1 cell Adaptive Immunity Adjuvants, Immunologic Animals Biological Markers Cell Differentiation Cells, Cultured Dendritic Cells Glucocorticoids Interferon-gamma Interleukin-10 Interleukin-12 Mice Mice, Inbred C57BL NF-kappa B Phosphorylation Proto-Oncogene Proteins c-akt Receptors, Glucocorticoid Receptors, Thyroid Hormone T-Lymphocytes Triiodothyronine
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_0039128X_v77_n1-2_p67_Montesinos
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_0039128X_v77_n1-2_p67_Montesinos2023-10-03T14:49:30Z Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells Montesinos, M.M. Alamino, V.A. Mascanfroni, I.D. Susperreguy, S. Gigena, N. Masini-Repiso, A.M. Rabinovich, G.A. Pellizas, C.G. Dendritic cells Dexamethasone Thyroid hormone action dexamethasone glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 10 interleukin 12 liothyronine protein kinase B animal cell antiinflammatory activity article cell maturation controlled study cytokine production cytokine release dendritic cell drug effect drug mechanism female lymphocyte proliferation mouse nonhuman Th1 cell Adaptive Immunity Adjuvants, Immunologic Animals Biological Markers Cell Differentiation Cells, Cultured Dendritic Cells Dexamethasone Glucocorticoids Interferon-gamma Interleukin-10 Interleukin-12 Mice Mice, Inbred C57BL NF-kappa B Phosphorylation Proto-Oncogene Proteins c-akt Receptors, Glucocorticoid Receptors, Thyroid Hormone T-Lymphocytes Triiodothyronine Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive agents. Several studies have indicated the important role of dendritic cells (DCs), highly specialized antigen-presenting and immunomodulatory cells, in GC-mediated suppression of adaptive immune responses. Recently, we demonstrated that triiodothyronine (T3) has potent immunostimulatory effects on bone marrow-derived mouse DCs through a mechanism involving T3 binding to cytosolic thyroid hormone receptor (TR) β1, rapid and sustained Akt activation and IL-12 production. Here we explored the impact of GCs on T3-mediated DC maturation and function and the intracellular events underlying these effects. Dexamethasone (Dex), a synthetic GC, potently inhibited T3-induced stimulation of DCs by preventing the augmented expression of maturation markers and the enhanced IL-12 secretion through mechanisms involving the GC receptor. These effects were accompanied by increased IL-10 levels following exposure of T3-conditioned DCs to Dex. Accordingly, Dex inhibited the immunostimulatory capacity of T3-matured DCs on naive T-cell proliferation and IFN-γ production while increased IL-10 synthesis by allogeneic T cell cultures. A mechanistic analysis revealed the ability of Dex to dampen T3 responses through modulation of Akt phosphorylation and cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). In addition, Dex decreased TRβ1 expression in both immature and T3-maturated DCs through mechanisms involving the GC receptor. Thus GCs, which are increased during the resolution of inflammatory responses, counteract the immunostimulatory effects of T3 on DCs and their ability to polarize adaptive immune responses toward a T helper (Th)-1-type through mechanisms involving, at least in part, NF-κB- and TRβ1-dependent pathways. Our data provide an alternative mechanism for the anti-inflammatory effects of GCs with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits. © 2011 Elsevier Inc. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0039128X_v77_n1-2_p67_Montesinos
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Dendritic cells Dexamethasone Thyroid hormone action dexamethasone glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 10 interleukin 12 liothyronine protein kinase B animal cell antiinflammatory activity article cell maturation controlled study cytokine production cytokine release dendritic cell drug effect drug mechanism female lymphocyte proliferation mouse nonhuman Th1 cell Adaptive Immunity Adjuvants, Immunologic Animals Biological Markers Cell Differentiation Cells, Cultured Dendritic Cells Dexamethasone Glucocorticoids Interferon-gamma Interleukin-10 Interleukin-12 Mice Mice, Inbred C57BL NF-kappa B Phosphorylation Proto-Oncogene Proteins c-akt Receptors, Glucocorticoid Receptors, Thyroid Hormone T-Lymphocytes Triiodothyronine
spellingShingle	Dendritic cells Dexamethasone Thyroid hormone action dexamethasone glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 10 interleukin 12 liothyronine protein kinase B animal cell antiinflammatory activity article cell maturation controlled study cytokine production cytokine release dendritic cell drug effect drug mechanism female lymphocyte proliferation mouse nonhuman Th1 cell Adaptive Immunity Adjuvants, Immunologic Animals Biological Markers Cell Differentiation Cells, Cultured Dendritic Cells Dexamethasone Glucocorticoids Interferon-gamma Interleukin-10 Interleukin-12 Mice Mice, Inbred C57BL NF-kappa B Phosphorylation Proto-Oncogene Proteins c-akt Receptors, Glucocorticoid Receptors, Thyroid Hormone T-Lymphocytes Triiodothyronine Montesinos, M.M. Alamino, V.A. Mascanfroni, I.D. Susperreguy, S. Gigena, N. Masini-Repiso, A.M. Rabinovich, G.A. Pellizas, C.G. Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
topic_facet	Dendritic cells Dexamethasone Thyroid hormone action dexamethasone glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 10 interleukin 12 liothyronine protein kinase B animal cell antiinflammatory activity article cell maturation controlled study cytokine production cytokine release dendritic cell drug effect drug mechanism female lymphocyte proliferation mouse nonhuman Th1 cell Adaptive Immunity Adjuvants, Immunologic Animals Biological Markers Cell Differentiation Cells, Cultured Dendritic Cells Dexamethasone Glucocorticoids Interferon-gamma Interleukin-10 Interleukin-12 Mice Mice, Inbred C57BL NF-kappa B Phosphorylation Proto-Oncogene Proteins c-akt Receptors, Glucocorticoid Receptors, Thyroid Hormone T-Lymphocytes Triiodothyronine
description	Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive agents. Several studies have indicated the important role of dendritic cells (DCs), highly specialized antigen-presenting and immunomodulatory cells, in GC-mediated suppression of adaptive immune responses. Recently, we demonstrated that triiodothyronine (T3) has potent immunostimulatory effects on bone marrow-derived mouse DCs through a mechanism involving T3 binding to cytosolic thyroid hormone receptor (TR) β1, rapid and sustained Akt activation and IL-12 production. Here we explored the impact of GCs on T3-mediated DC maturation and function and the intracellular events underlying these effects. Dexamethasone (Dex), a synthetic GC, potently inhibited T3-induced stimulation of DCs by preventing the augmented expression of maturation markers and the enhanced IL-12 secretion through mechanisms involving the GC receptor. These effects were accompanied by increased IL-10 levels following exposure of T3-conditioned DCs to Dex. Accordingly, Dex inhibited the immunostimulatory capacity of T3-matured DCs on naive T-cell proliferation and IFN-γ production while increased IL-10 synthesis by allogeneic T cell cultures. A mechanistic analysis revealed the ability of Dex to dampen T3 responses through modulation of Akt phosphorylation and cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). In addition, Dex decreased TRβ1 expression in both immature and T3-maturated DCs through mechanisms involving the GC receptor. Thus GCs, which are increased during the resolution of inflammatory responses, counteract the immunostimulatory effects of T3 on DCs and their ability to polarize adaptive immune responses toward a T helper (Th)-1-type through mechanisms involving, at least in part, NF-κB- and TRβ1-dependent pathways. Our data provide an alternative mechanism for the anti-inflammatory effects of GCs with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits. © 2011 Elsevier Inc. All rights reserved.
format	JOUR
author	Montesinos, M.M. Alamino, V.A. Mascanfroni, I.D. Susperreguy, S. Gigena, N. Masini-Repiso, A.M. Rabinovich, G.A. Pellizas, C.G.
author_facet	Montesinos, M.M. Alamino, V.A. Mascanfroni, I.D. Susperreguy, S. Gigena, N. Masini-Repiso, A.M. Rabinovich, G.A. Pellizas, C.G.
author_sort	Montesinos, M.M.
title	Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
title_short	Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
title_full	Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
title_fullStr	Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
title_full_unstemmed	Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
title_sort	dexamethasone counteracts the immunostimulatory effects of triiodothyronine (t3) on dendritic cells
url	http://hdl.handle.net/20.500.12110/paper_0039128X_v77_n1-2_p67_Montesinos
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_version_	1807319432727363584

Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells

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