TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis

Autores
Cargnelutti, Ethelina; Arias, Jose Luis; Valdez, Susana Ruth; Rabinovich, Gabriel Adrián; Di Genaro, Maria Silvia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In addition to its well-known pro-inflammatory effects, tumor necrosis factor (TNF) displays anti-inflammatory activities through mechanisms poorly understood. Previously, we reported the development of severe chronic Yersinia enterocolitica-induced reactive arthritis (ReA) in mice lacking the TNF receptor (TNFR)p55. As regulatory T (Treg) cells limit chronic inflammation, here we aim to investigate the expansion and function of CD4 þ CD25 þ FoxP3 þ Treg cells in the ReA animal model. The number of Treg cells as well as the FoxP3 mRNA expression and interleukin (IL)-10 levels were significantly decreased in joint regional lymph nodes (RLNs) of TNFRp55 / mice vs wild-type (WT) mice at the arthritis onset. However, at chronic phase of arthritis, the number of Treg cell in TNFRp55 / was similar to WT mice. To explore the in vivo function of Treg cells at this chronic phase in WT and TNFRp55-deficient mice, we adoptively transferred CD4 þ T cells from TNFRp55-deficient mice of day 21, into naı¨ve WT or TNFRp55 / mice. When knockout mice were used as recipients we observed higher delayed-type hypersensitivity (DTH) responses and joint inflammation after heat-killed Yersinia (HKY) stimulation. Accordingly, we found higher levels of IL-17, interferon (IFN)-c, IL-6, transforming growth factor-b1 and IL-12/23p40 and lower IL-10 levels in RLN of paws challenged with HKY in TNFRp55 / recipient mice. In addition, we found that CD4 þ T cells from TNFRp55 / mice controlled antigen-specific IL-12/23(p40) production in recipient WT mice. Our results show that TNFRp55 controls the induction and function of Treg cells through differential regulation of cytokine production, suggesting a novel molecular target for immune intervention in ReA.
Fil: Cargnelutti, Ethelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Arias, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Materia
Reactive-Arthritis
Regulatory-T-Cells
Tnf
Tnrfp55
Yersinia Enterocolitica
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:11336/2176
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/2176
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritisCargnelutti, EthelinaArias, Jose LuisValdez, Susana RuthRabinovich, Gabriel AdriánDi Genaro, Maria SilviaReactive-ArthritisRegulatory-T-CellsTnfTnrfp55Yersinia Enterocoliticahttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3In addition to its well-known pro-inflammatory effects, tumor necrosis factor (TNF) displays anti-inflammatory activities through mechanisms poorly understood. Previously, we reported the development of severe chronic Yersinia enterocolitica-induced reactive arthritis (ReA) in mice lacking the TNF receptor (TNFR)p55. As regulatory T (Treg) cells limit chronic inflammation, here we aim to investigate the expansion and function of CD4 þ CD25 þ FoxP3 þ Treg cells in the ReA animal model. The number of Treg cells as well as the FoxP3 mRNA expression and interleukin (IL)-10 levels were significantly decreased in joint regional lymph nodes (RLNs) of TNFRp55 / mice vs wild-type (WT) mice at the arthritis onset. However, at chronic phase of arthritis, the number of Treg cell in TNFRp55 / was similar to WT mice. To explore the in vivo function of Treg cells at this chronic phase in WT and TNFRp55-deficient mice, we adoptively transferred CD4 þ T cells from TNFRp55-deficient mice of day 21, into naı¨ve WT or TNFRp55 / mice. When knockout mice were used as recipients we observed higher delayed-type hypersensitivity (DTH) responses and joint inflammation after heat-killed Yersinia (HKY) stimulation. Accordingly, we found higher levels of IL-17, interferon (IFN)-c, IL-6, transforming growth factor-b1 and IL-12/23p40 and lower IL-10 levels in RLN of paws challenged with HKY in TNFRp55 / recipient mice. In addition, we found that CD4 þ T cells from TNFRp55 / mice controlled antigen-specific IL-12/23(p40) production in recipient WT mice. Our results show that TNFRp55 controls the induction and function of Treg cells through differential regulation of cytokine production, suggesting a novel molecular target for immune intervention in ReA.Fil: Cargnelutti, Ethelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Arias, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaNature Publishing Group2013-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2176Cargnelutti, Ethelina; Arias, Jose Luis; Valdez, Susana Ruth; Rabinovich, Gabriel Adrián; Di Genaro, Maria Silvia; TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis; Nature Publishing Group; Immunology and Cell Biology; 91; 2-2013; 159-1660818-9641enginfo:eu-repo/semantics/altIdentifier/doi/doi:10.1038/icb.2012.65info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/icb/journal/v91/n2/full/icb201265a.htmlinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:31:53Zoai:ri.conicet.gov.ar:11336/2176instacron: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:34982025-10-22 11:31:53.714CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis
title TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis
spellingShingle TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis
Cargnelutti, Ethelina
Reactive-Arthritis
Regulatory-T-Cells
Tnf
Tnrfp55
Yersinia Enterocolitica
title_short TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis
title_full TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis
title_fullStr TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis
title_full_unstemmed TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis
title_sort TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis
dc.creator.none.fl_str_mv Cargnelutti, Ethelina
Arias, Jose Luis
Valdez, Susana Ruth
Rabinovich, Gabriel Adrián
Di Genaro, Maria Silvia
author Cargnelutti, Ethelina
author_facet Cargnelutti, Ethelina
Arias, Jose Luis
Valdez, Susana Ruth
Rabinovich, Gabriel Adrián
Di Genaro, Maria Silvia
author_role author
author2 Arias, Jose Luis
Valdez, Susana Ruth
Rabinovich, Gabriel Adrián
Di Genaro, Maria Silvia
author2_role author
author
author
author
dc.subject.none.fl_str_mv Reactive-Arthritis
Regulatory-T-Cells
Tnf
Tnrfp55
Yersinia Enterocolitica
topic Reactive-Arthritis
Regulatory-T-Cells
Tnf
Tnrfp55
Yersinia Enterocolitica
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In addition to its well-known pro-inflammatory effects, tumor necrosis factor (TNF) displays anti-inflammatory activities through mechanisms poorly understood. Previously, we reported the development of severe chronic Yersinia enterocolitica-induced reactive arthritis (ReA) in mice lacking the TNF receptor (TNFR)p55. As regulatory T (Treg) cells limit chronic inflammation, here we aim to investigate the expansion and function of CD4 þ CD25 þ FoxP3 þ Treg cells in the ReA animal model. The number of Treg cells as well as the FoxP3 mRNA expression and interleukin (IL)-10 levels were significantly decreased in joint regional lymph nodes (RLNs) of TNFRp55 / mice vs wild-type (WT) mice at the arthritis onset. However, at chronic phase of arthritis, the number of Treg cell in TNFRp55 / was similar to WT mice. To explore the in vivo function of Treg cells at this chronic phase in WT and TNFRp55-deficient mice, we adoptively transferred CD4 þ T cells from TNFRp55-deficient mice of day 21, into naı¨ve WT or TNFRp55 / mice. When knockout mice were used as recipients we observed higher delayed-type hypersensitivity (DTH) responses and joint inflammation after heat-killed Yersinia (HKY) stimulation. Accordingly, we found higher levels of IL-17, interferon (IFN)-c, IL-6, transforming growth factor-b1 and IL-12/23p40 and lower IL-10 levels in RLN of paws challenged with HKY in TNFRp55 / recipient mice. In addition, we found that CD4 þ T cells from TNFRp55 / mice controlled antigen-specific IL-12/23(p40) production in recipient WT mice. Our results show that TNFRp55 controls the induction and function of Treg cells through differential regulation of cytokine production, suggesting a novel molecular target for immune intervention in ReA.
Fil: Cargnelutti, Ethelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Arias, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigación Biológica de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
description In addition to its well-known pro-inflammatory effects, tumor necrosis factor (TNF) displays anti-inflammatory activities through mechanisms poorly understood. Previously, we reported the development of severe chronic Yersinia enterocolitica-induced reactive arthritis (ReA) in mice lacking the TNF receptor (TNFR)p55. As regulatory T (Treg) cells limit chronic inflammation, here we aim to investigate the expansion and function of CD4 þ CD25 þ FoxP3 þ Treg cells in the ReA animal model. The number of Treg cells as well as the FoxP3 mRNA expression and interleukin (IL)-10 levels were significantly decreased in joint regional lymph nodes (RLNs) of TNFRp55 / mice vs wild-type (WT) mice at the arthritis onset. However, at chronic phase of arthritis, the number of Treg cell in TNFRp55 / was similar to WT mice. To explore the in vivo function of Treg cells at this chronic phase in WT and TNFRp55-deficient mice, we adoptively transferred CD4 þ T cells from TNFRp55-deficient mice of day 21, into naı¨ve WT or TNFRp55 / mice. When knockout mice were used as recipients we observed higher delayed-type hypersensitivity (DTH) responses and joint inflammation after heat-killed Yersinia (HKY) stimulation. Accordingly, we found higher levels of IL-17, interferon (IFN)-c, IL-6, transforming growth factor-b1 and IL-12/23p40 and lower IL-10 levels in RLN of paws challenged with HKY in TNFRp55 / recipient mice. In addition, we found that CD4 þ T cells from TNFRp55 / mice controlled antigen-specific IL-12/23(p40) production in recipient WT mice. Our results show that TNFRp55 controls the induction and function of Treg cells through differential regulation of cytokine production, suggesting a novel molecular target for immune intervention in ReA.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
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/11336/2176
Cargnelutti, Ethelina; Arias, Jose Luis; Valdez, Susana Ruth; Rabinovich, Gabriel Adrián; Di Genaro, Maria Silvia; TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis; Nature Publishing Group; Immunology and Cell Biology; 91; 2-2013; 159-166
0818-9641
url http://hdl.handle.net/11336/2176
identifier_str_mv Cargnelutti, Ethelina; Arias, Jose Luis; Valdez, Susana Ruth; Rabinovich, Gabriel Adrián; Di Genaro, Maria Silvia; TNFRp55 controls regulatory T cell responses in Yersinia-induced reactive arthritis; Nature Publishing Group; Immunology and Cell Biology; 91; 2-2013; 159-166
0818-9641
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/doi:10.1038/icb.2012.65
info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/icb/journal/v91/n2/full/icb201265a.html
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
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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