Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis

Autores
Eliçabe, Ricardo Javier; Cargnelutti, Ethelina; Serer, María Inés; Stege, Patricia Wanda; Valdez, Susana Ruth; Toscano, Marta Alicia; Rabinovich, Gabriel Adrián; Di Genaro, Maria Silvia
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Reactive arthritis (ReA) is a type of arthritis originating from certain gastrointestinal or genitourinary infections. In previous studies, we reported the development of progressive Yersinia enterocolitica-induced ReA in mice lacking TNFR p55; however, the mechanisms underlying this effect are still uncertain. In this study, we investigated the impact of TNFR p55 deficiency in modulating Ag-specific Th1 and Th17 responses during this arthritogenic process. We found more severe ReA in TNFRp55-/- mice compared with their wild-type (WT) counterparts. This effect was accompanied by increased levels of Yersinia LPS in the joints of knockout mice. Analysis of the local cytokine profile revealed greater amounts of IFN-γ and IL-17 in arthritic joints of TNFRp55-/- mice compared with WT mice at day 21 postinfection. Moreover, altered IL-17 and IFN-γ production was observed in mesenteric and inguinal lymph nodes of Yersinia-infected TNFRp55-/- mice, as well as in spleen cells obtained from infected mice and restimulated ex vivo with bacterial Ags. Increased levels of cytokine secretion were associated with a greater frequency of CD4+ IL-17+, CD4 +IFN-γ+, and IL-17+IFN- γ+ cells in TNFRp55-/-mice compared with WT mice. Remarkably, Ab-mediated blockade of IL-17 and/or IFN-γ resulted in reduced joint histological scores in TNFRp55-/- mice. A mechanistic analysis revealed the involvement of p40, a common subunit of heterodimeric IL-12 and IL-23, in the generation of augmented IFN-γ and IL-17 production under TNFR p55 deficiency. Taken together, these data indicate that, in the absence of TNFR p55 signaling, Th1 and Th17 effector cells may act in concert to sustain the inflammatory response in bacterial-induced arthritogenic processes.
Fil: Eliçabe, Ricardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Cargnelutti, Ethelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Serer, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Stege, Patricia Wanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina; Argentina
Fil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo; Argentina
Fil: Toscano, Marta Alicia. 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
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; Argentina
Fil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
Rodent
Cytokine receptors
Cytokines
Bacterial infection
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:11336/95979
Acceder
id CONICETDig_b1630e451f9814f677f0a268571c6061
oai_identifier_str oai:ri.conicet.gov.ar:11336/95979
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritisEliçabe, Ricardo JavierCargnelutti, EthelinaSerer, María InésStege, Patricia WandaValdez, Susana RuthToscano, Marta AliciaRabinovich, Gabriel AdriánDi Genaro, Maria SilviaRodentCytokine receptorsCytokinesBacterial infectionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Reactive arthritis (ReA) is a type of arthritis originating from certain gastrointestinal or genitourinary infections. In previous studies, we reported the development of progressive Yersinia enterocolitica-induced ReA in mice lacking TNFR p55; however, the mechanisms underlying this effect are still uncertain. In this study, we investigated the impact of TNFR p55 deficiency in modulating Ag-specific Th1 and Th17 responses during this arthritogenic process. We found more severe ReA in TNFRp55-/- mice compared with their wild-type (WT) counterparts. This effect was accompanied by increased levels of Yersinia LPS in the joints of knockout mice. Analysis of the local cytokine profile revealed greater amounts of IFN-γ and IL-17 in arthritic joints of TNFRp55-/- mice compared with WT mice at day 21 postinfection. Moreover, altered IL-17 and IFN-γ production was observed in mesenteric and inguinal lymph nodes of Yersinia-infected TNFRp55-/- mice, as well as in spleen cells obtained from infected mice and restimulated ex vivo with bacterial Ags. Increased levels of cytokine secretion were associated with a greater frequency of CD4+ IL-17+, CD4 +IFN-γ+, and IL-17+IFN- γ+ cells in TNFRp55-/-mice compared with WT mice. Remarkably, Ab-mediated blockade of IL-17 and/or IFN-γ resulted in reduced joint histological scores in TNFRp55-/- mice. A mechanistic analysis revealed the involvement of p40, a common subunit of heterodimeric IL-12 and IL-23, in the generation of augmented IFN-γ and IL-17 production under TNFR p55 deficiency. Taken together, these data indicate that, in the absence of TNFR p55 signaling, Th1 and Th17 effector cells may act in concert to sustain the inflammatory response in bacterial-induced arthritogenic processes.Fil: Eliçabe, Ricardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Cargnelutti, Ethelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Serer, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Stege, Patricia Wanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina; ArgentinaFil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Toscano, Marta Alicia. 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; 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; ArgentinaFil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaAmerican Association of Immunologists2010-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95979Eliçabe, Ricardo Javier; Cargnelutti, Ethelina; Serer, María Inés; Stege, Patricia Wanda; Valdez, Susana Ruth; et al.; Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis; American Association of Immunologists; Journal of Immunology; 185; 7; 10-2010; 4485-44950022-1767CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.0902245info:eu-repo/semantics/altIdentifier/url/https://www.jimmunol.org/content/185/7/4485.longinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:58:34Zoai:ri.conicet.gov.ar:11336/95979instacron: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 14:58:34.579CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis
title Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis
spellingShingle Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis
Eliçabe, Ricardo Javier
Rodent
Cytokine receptors
Cytokines
Bacterial infection
title_short Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis
title_full Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis
title_fullStr Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis
title_full_unstemmed Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis
title_sort Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis
dc.creator.none.fl_str_mv Eliçabe, Ricardo Javier
Cargnelutti, Ethelina
Serer, María Inés
Stege, Patricia Wanda
Valdez, Susana Ruth
Toscano, Marta Alicia
Rabinovich, Gabriel Adrián
Di Genaro, Maria Silvia
author Eliçabe, Ricardo Javier
author_facet Eliçabe, Ricardo Javier
Cargnelutti, Ethelina
Serer, María Inés
Stege, Patricia Wanda
Valdez, Susana Ruth
Toscano, Marta Alicia
Rabinovich, Gabriel Adrián
Di Genaro, Maria Silvia
author_role author
author2 Cargnelutti, Ethelina
Serer, María Inés
Stege, Patricia Wanda
Valdez, Susana Ruth
Toscano, Marta Alicia
Rabinovich, Gabriel Adrián
Di Genaro, Maria Silvia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Rodent
Cytokine receptors
Cytokines
Bacterial infection
topic Rodent
Cytokine receptors
Cytokines
Bacterial infection
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Reactive arthritis (ReA) is a type of arthritis originating from certain gastrointestinal or genitourinary infections. In previous studies, we reported the development of progressive Yersinia enterocolitica-induced ReA in mice lacking TNFR p55; however, the mechanisms underlying this effect are still uncertain. In this study, we investigated the impact of TNFR p55 deficiency in modulating Ag-specific Th1 and Th17 responses during this arthritogenic process. We found more severe ReA in TNFRp55-/- mice compared with their wild-type (WT) counterparts. This effect was accompanied by increased levels of Yersinia LPS in the joints of knockout mice. Analysis of the local cytokine profile revealed greater amounts of IFN-γ and IL-17 in arthritic joints of TNFRp55-/- mice compared with WT mice at day 21 postinfection. Moreover, altered IL-17 and IFN-γ production was observed in mesenteric and inguinal lymph nodes of Yersinia-infected TNFRp55-/- mice, as well as in spleen cells obtained from infected mice and restimulated ex vivo with bacterial Ags. Increased levels of cytokine secretion were associated with a greater frequency of CD4+ IL-17+, CD4 +IFN-γ+, and IL-17+IFN- γ+ cells in TNFRp55-/-mice compared with WT mice. Remarkably, Ab-mediated blockade of IL-17 and/or IFN-γ resulted in reduced joint histological scores in TNFRp55-/- mice. A mechanistic analysis revealed the involvement of p40, a common subunit of heterodimeric IL-12 and IL-23, in the generation of augmented IFN-γ and IL-17 production under TNFR p55 deficiency. Taken together, these data indicate that, in the absence of TNFR p55 signaling, Th1 and Th17 effector cells may act in concert to sustain the inflammatory response in bacterial-induced arthritogenic processes.
Fil: Eliçabe, Ricardo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Cargnelutti, Ethelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Serer, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Stege, Patricia Wanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina; Argentina
Fil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo; Argentina
Fil: Toscano, Marta Alicia. 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
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; Argentina
Fil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description Reactive arthritis (ReA) is a type of arthritis originating from certain gastrointestinal or genitourinary infections. In previous studies, we reported the development of progressive Yersinia enterocolitica-induced ReA in mice lacking TNFR p55; however, the mechanisms underlying this effect are still uncertain. In this study, we investigated the impact of TNFR p55 deficiency in modulating Ag-specific Th1 and Th17 responses during this arthritogenic process. We found more severe ReA in TNFRp55-/- mice compared with their wild-type (WT) counterparts. This effect was accompanied by increased levels of Yersinia LPS in the joints of knockout mice. Analysis of the local cytokine profile revealed greater amounts of IFN-γ and IL-17 in arthritic joints of TNFRp55-/- mice compared with WT mice at day 21 postinfection. Moreover, altered IL-17 and IFN-γ production was observed in mesenteric and inguinal lymph nodes of Yersinia-infected TNFRp55-/- mice, as well as in spleen cells obtained from infected mice and restimulated ex vivo with bacterial Ags. Increased levels of cytokine secretion were associated with a greater frequency of CD4+ IL-17+, CD4 +IFN-γ+, and IL-17+IFN- γ+ cells in TNFRp55-/-mice compared with WT mice. Remarkably, Ab-mediated blockade of IL-17 and/or IFN-γ resulted in reduced joint histological scores in TNFRp55-/- mice. A mechanistic analysis revealed the involvement of p40, a common subunit of heterodimeric IL-12 and IL-23, in the generation of augmented IFN-γ and IL-17 production under TNFR p55 deficiency. Taken together, these data indicate that, in the absence of TNFR p55 signaling, Th1 and Th17 effector cells may act in concert to sustain the inflammatory response in bacterial-induced arthritogenic processes.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
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/11336/95979
Eliçabe, Ricardo Javier; Cargnelutti, Ethelina; Serer, María Inés; Stege, Patricia Wanda; Valdez, Susana Ruth; et al.; Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis; American Association of Immunologists; Journal of Immunology; 185; 7; 10-2010; 4485-4495
0022-1767
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95979
identifier_str_mv Eliçabe, Ricardo Javier; Cargnelutti, Ethelina; Serer, María Inés; Stege, Patricia Wanda; Valdez, Susana Ruth; et al.; Lack of TNFR p55 results in heightened expression of ifn-γ and IL-17 during the development of reactive arthritis; American Association of Immunologists; Journal of Immunology; 185; 7; 10-2010; 4485-4495
0022-1767
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.0902245
info:eu-repo/semantics/altIdentifier/url/https://www.jimmunol.org/content/185/7/4485.long
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 American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
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 13.221938

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