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

Autores
Montesinos, Maria del Mar; Alamino, Vanina Alejandra; Mascanfroni, Ivan Darío; Susperreguy, Sebastian; Gigena, Nicolás; Masini, Ana María; Rabinovich, Gabriel Adrián; Pellizas, Claudia Gabriela
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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) betha 1,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-gamma 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-kB (NF-kB). In addition,Dex decreased TRb1 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-kB- and TRb1-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.
Fil: Montesinos, Maria del Mar. Universidad Nacional de Córdoba; Argentina
Fil: Alamino, Vanina Alejandra. Universidad Nacional de Córdoba; Argentina
Fil: Mascanfroni, Ivan Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad Nacional de Córdoba; Argentina
Fil: Susperreguy, Sebastian. Universidad Nacional de Córdoba; Argentina
Fil: Gigena, Nicolás. Universidad Nacional de Córdoba; Argentina
Fil: Masini, Ana María. Universidad Nacional de Córdoba; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires; Argentina
Fil: Pellizas, Claudia Gabriela. Universidad Nacional de Córdoba; Argentina
Materia
DEXAMETHASONE
THYROID HORMONE ACTION
DENDRITIC CELLS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/84568
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/84568
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cellsMontesinos, Maria del MarAlamino, Vanina AlejandraMascanfroni, Ivan DaríoSusperreguy, SebastianGigena, NicolásMasini, Ana MaríaRabinovich, Gabriel AdriánPellizas, Claudia GabrielaDEXAMETHASONETHYROID HORMONE ACTIONDENDRITIC CELLShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Glucocorticoids (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) betha 1,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-gamma 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-kB (NF-kB). In addition,Dex decreased TRb1 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-kB- and TRb1-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.Fil: Montesinos, Maria del Mar. Universidad Nacional de Córdoba; ArgentinaFil: Alamino, Vanina Alejandra. Universidad Nacional de Córdoba; ArgentinaFil: Mascanfroni, Ivan Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Susperreguy, Sebastian. Universidad Nacional de Córdoba; ArgentinaFil: Gigena, Nicolás. Universidad Nacional de Córdoba; ArgentinaFil: Masini, Ana María. Universidad Nacional de Córdoba; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires; ArgentinaFil: Pellizas, Claudia Gabriela. Universidad Nacional de Córdoba; ArgentinaElsevier Science Inc2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/84568Montesinos, Maria del Mar; Alamino, Vanina Alejandra; Mascanfroni, Ivan Darío; Susperreguy, Sebastian; Gigena, Nicolás; et al.; Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells; Elsevier Science Inc; Steroids; 77; 1-2; 1-2012; 67-760039-128XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.steroids.2011.10.006info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0039128X11003102?via%3Dihubinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:25:58Zoai:ri.conicet.gov.ar:11336/84568instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:25:58.57CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
title Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
spellingShingle Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
Montesinos, Maria del Mar
DEXAMETHASONE
THYROID HORMONE ACTION
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
dc.creator.none.fl_str_mv Montesinos, Maria del Mar
Alamino, Vanina Alejandra
Mascanfroni, Ivan Darío
Susperreguy, Sebastian
Gigena, Nicolás
Masini, Ana María
Rabinovich, Gabriel Adrián
Pellizas, Claudia Gabriela
author Montesinos, Maria del Mar
author_facet Montesinos, Maria del Mar
Alamino, Vanina Alejandra
Mascanfroni, Ivan Darío
Susperreguy, Sebastian
Gigena, Nicolás
Masini, Ana María
Rabinovich, Gabriel Adrián
Pellizas, Claudia Gabriela
author_role author
author2 Alamino, Vanina Alejandra
Mascanfroni, Ivan Darío
Susperreguy, Sebastian
Gigena, Nicolás
Masini, Ana María
Rabinovich, Gabriel Adrián
Pellizas, Claudia Gabriela
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DEXAMETHASONE
THYROID HORMONE ACTION
DENDRITIC CELLS
topic DEXAMETHASONE
THYROID HORMONE ACTION
DENDRITIC CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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) betha 1,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-gamma 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-kB (NF-kB). In addition,Dex decreased TRb1 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-kB- and TRb1-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.
Fil: Montesinos, Maria del Mar. Universidad Nacional de Córdoba; Argentina
Fil: Alamino, Vanina Alejandra. Universidad Nacional de Córdoba; Argentina
Fil: Mascanfroni, Ivan Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad Nacional de Córdoba; Argentina
Fil: Susperreguy, Sebastian. Universidad Nacional de Córdoba; Argentina
Fil: Gigena, Nicolás. Universidad Nacional de Córdoba; Argentina
Fil: Masini, Ana María. Universidad Nacional de Córdoba; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires; Argentina
Fil: Pellizas, Claudia Gabriela. Universidad Nacional de Córdoba; Argentina
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) betha 1,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-gamma 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-kB (NF-kB). In addition,Dex decreased TRb1 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-kB- and TRb1-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.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/84568
Montesinos, Maria del Mar; Alamino, Vanina Alejandra; Mascanfroni, Ivan Darío; Susperreguy, Sebastian; Gigena, Nicolás; et al.; Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells; Elsevier Science Inc; Steroids; 77; 1-2; 1-2012; 67-76
0039-128X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/84568
identifier_str_mv Montesinos, Maria del Mar; Alamino, Vanina Alejandra; Mascanfroni, Ivan Darío; Susperreguy, Sebastian; Gigena, Nicolás; et al.; Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells; Elsevier Science Inc; Steroids; 77; 1-2; 1-2012; 67-76
0039-128X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.steroids.2011.10.006
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0039128X11003102?via%3Dihub
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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