TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes

Autores
Staniek, Julian; Lorenzetti, Raquel; Heller, Bianca; Janowska, Iga; Schneider, Pascal; Unger, Susanne; Warnatz, Klaus; Seidl, Maximilian; Venhoff, Nils; Thiel, Jens; Smulski, Cristian Roberto; Rizzi, Marta
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The maintenance of B cell homeostasis requires a tight control of B cell generation, survival, activation, and maturation. In lymphocytes upon activation, increased sensitivity to apoptotic signals helps controlling differentiation and proliferation. The death receptor Fas is important in this context because genetic Fas mutations in humans lead to an autoimmune lymphoproliferative syndrome that is similar to lymphoproliferation observed in Fas-deficient mice. In contrast, the physiological role of TNF-related apoptosis-inducing ligand receptors (TRAIL-Rs) in humans has been poorly studied so far. Indeed, most studies have focused on tumor cell lines and on mouse models whose results are difficult to transpose to primary human B cells. In the present work, the expression of apoptosis-inducing TRAIL-R1 and TRAIL-R2 and of the decoy receptors TRAIL-R3 and TRAIL-R4 was systematically studied in all developmental stages of peripheral B cells isolated from the blood and secondary lymphoid organs. Expression of TRAIL-Rs is modulated along development, with highest levels observed in germinal center B cells. In addition, T-dependent and T-independent signals elicited induction of TRAIL-Rs with distinct kinetics, which differed among B cell subpopulations: switched memory cells rapidly upregulated TRAIL-R1 and -2 upon activation while naïve B cells only reached similar expression levels at later time points in culture. Increased expression of TRAIL-R1 and -2 coincided with a caspase-3-dependent sensitivity to TRAIL-induced apoptosis in activated B cells but not in freshly isolated resting B cells. Finally, both TRAIL-R1 and TRAIL-R2 could signal actively and both contributed to TRAIL-induced apoptosis. In conclusion, this study provides a systematic analysis of the expression of TRAIL-Rs in human primary B cells and of their capacity to signal and induce apoptosis. This dataset forms a basis to further study and understand the dysregulation of TRAIL-Rs and TRAIL expression observed in autoimmune diseases. Additionally, it will be important to foresee potential bystander immunomodulation when TRAIL-R agonists are used in cancer treatment.
Fil: Staniek, Julian. Albert Ludwigs University of Freiburg; Alemania
Fil: Lorenzetti, Raquel. Albert Ludwigs University of Freiburg; Alemania
Fil: Heller, Bianca. Albert Ludwigs University of Freiburg; Alemania
Fil: Janowska, Iga. Albert Ludwigs University of Freiburg; Alemania
Fil: Schneider, Pascal. Universite de Lausanne; Suiza
Fil: Unger, Susanne. Albert Ludwigs University of Freiburg; Alemania
Fil: Warnatz, Klaus. Albert Ludwigs University of Freiburg; Alemania
Fil: Seidl, Maximilian. Albert Ludwigs University of Freiburg; Alemania
Fil: Venhoff, Nils. Albert Ludwigs University of Freiburg; Alemania
Fil: Thiel, Jens. Albert Ludwigs University of Freiburg; Alemania
Fil: Smulski, Cristian Roberto. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina
Fil: Rizzi, Marta. Albert Ludwigs University of Freiburg; Alemania
Materia
APOPTOSIS
B LYMPHOCYTES
HUMAN
TRAIL
TRAIL-R
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/174901
Acceder
id CONICETDig_4404004158689647ec6f4ea788572882
oai_identifier_str oai:ri.conicet.gov.ar:11336/174901
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytesStaniek, JulianLorenzetti, RaquelHeller, BiancaJanowska, IgaSchneider, PascalUnger, SusanneWarnatz, KlausSeidl, MaximilianVenhoff, NilsThiel, JensSmulski, Cristian RobertoRizzi, MartaAPOPTOSISB LYMPHOCYTESHUMANTRAILTRAIL-Rhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The maintenance of B cell homeostasis requires a tight control of B cell generation, survival, activation, and maturation. In lymphocytes upon activation, increased sensitivity to apoptotic signals helps controlling differentiation and proliferation. The death receptor Fas is important in this context because genetic Fas mutations in humans lead to an autoimmune lymphoproliferative syndrome that is similar to lymphoproliferation observed in Fas-deficient mice. In contrast, the physiological role of TNF-related apoptosis-inducing ligand receptors (TRAIL-Rs) in humans has been poorly studied so far. Indeed, most studies have focused on tumor cell lines and on mouse models whose results are difficult to transpose to primary human B cells. In the present work, the expression of apoptosis-inducing TRAIL-R1 and TRAIL-R2 and of the decoy receptors TRAIL-R3 and TRAIL-R4 was systematically studied in all developmental stages of peripheral B cells isolated from the blood and secondary lymphoid organs. Expression of TRAIL-Rs is modulated along development, with highest levels observed in germinal center B cells. In addition, T-dependent and T-independent signals elicited induction of TRAIL-Rs with distinct kinetics, which differed among B cell subpopulations: switched memory cells rapidly upregulated TRAIL-R1 and -2 upon activation while naïve B cells only reached similar expression levels at later time points in culture. Increased expression of TRAIL-R1 and -2 coincided with a caspase-3-dependent sensitivity to TRAIL-induced apoptosis in activated B cells but not in freshly isolated resting B cells. Finally, both TRAIL-R1 and TRAIL-R2 could signal actively and both contributed to TRAIL-induced apoptosis. In conclusion, this study provides a systematic analysis of the expression of TRAIL-Rs in human primary B cells and of their capacity to signal and induce apoptosis. This dataset forms a basis to further study and understand the dysregulation of TRAIL-Rs and TRAIL expression observed in autoimmune diseases. Additionally, it will be important to foresee potential bystander immunomodulation when TRAIL-R agonists are used in cancer treatment.Fil: Staniek, Julian. Albert Ludwigs University of Freiburg; AlemaniaFil: Lorenzetti, Raquel. Albert Ludwigs University of Freiburg; AlemaniaFil: Heller, Bianca. Albert Ludwigs University of Freiburg; AlemaniaFil: Janowska, Iga. Albert Ludwigs University of Freiburg; AlemaniaFil: Schneider, Pascal. Universite de Lausanne; SuizaFil: Unger, Susanne. Albert Ludwigs University of Freiburg; AlemaniaFil: Warnatz, Klaus. Albert Ludwigs University of Freiburg; AlemaniaFil: Seidl, Maximilian. Albert Ludwigs University of Freiburg; AlemaniaFil: Venhoff, Nils. Albert Ludwigs University of Freiburg; AlemaniaFil: Thiel, Jens. Albert Ludwigs University of Freiburg; AlemaniaFil: Smulski, Cristian Roberto. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Rizzi, Marta. Albert Ludwigs University of Freiburg; AlemaniaFrontiers Media2019-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174901Staniek, Julian; Lorenzetti, Raquel; Heller, Bianca; Janowska, Iga; Schneider, Pascal; et al.; TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes; Frontiers Media; Frontiers in Immunology; 10; 4-2019; 1-131664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2019.00951/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.00951info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:00:12Zoai:ri.conicet.gov.ar:11336/174901instacron: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 12:00:12.681CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes
title TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes
spellingShingle TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes
Staniek, Julian
APOPTOSIS
B LYMPHOCYTES
HUMAN
TRAIL
TRAIL-R
title_short TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes
title_full TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes
title_fullStr TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes
title_full_unstemmed TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes
title_sort TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes
dc.creator.none.fl_str_mv Staniek, Julian
Lorenzetti, Raquel
Heller, Bianca
Janowska, Iga
Schneider, Pascal
Unger, Susanne
Warnatz, Klaus
Seidl, Maximilian
Venhoff, Nils
Thiel, Jens
Smulski, Cristian Roberto
Rizzi, Marta
author Staniek, Julian
author_facet Staniek, Julian
Lorenzetti, Raquel
Heller, Bianca
Janowska, Iga
Schneider, Pascal
Unger, Susanne
Warnatz, Klaus
Seidl, Maximilian
Venhoff, Nils
Thiel, Jens
Smulski, Cristian Roberto
Rizzi, Marta
author_role author
author2 Lorenzetti, Raquel
Heller, Bianca
Janowska, Iga
Schneider, Pascal
Unger, Susanne
Warnatz, Klaus
Seidl, Maximilian
Venhoff, Nils
Thiel, Jens
Smulski, Cristian Roberto
Rizzi, Marta
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv APOPTOSIS
B LYMPHOCYTES
HUMAN
TRAIL
TRAIL-R
topic APOPTOSIS
B LYMPHOCYTES
HUMAN
TRAIL
TRAIL-R
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The maintenance of B cell homeostasis requires a tight control of B cell generation, survival, activation, and maturation. In lymphocytes upon activation, increased sensitivity to apoptotic signals helps controlling differentiation and proliferation. The death receptor Fas is important in this context because genetic Fas mutations in humans lead to an autoimmune lymphoproliferative syndrome that is similar to lymphoproliferation observed in Fas-deficient mice. In contrast, the physiological role of TNF-related apoptosis-inducing ligand receptors (TRAIL-Rs) in humans has been poorly studied so far. Indeed, most studies have focused on tumor cell lines and on mouse models whose results are difficult to transpose to primary human B cells. In the present work, the expression of apoptosis-inducing TRAIL-R1 and TRAIL-R2 and of the decoy receptors TRAIL-R3 and TRAIL-R4 was systematically studied in all developmental stages of peripheral B cells isolated from the blood and secondary lymphoid organs. Expression of TRAIL-Rs is modulated along development, with highest levels observed in germinal center B cells. In addition, T-dependent and T-independent signals elicited induction of TRAIL-Rs with distinct kinetics, which differed among B cell subpopulations: switched memory cells rapidly upregulated TRAIL-R1 and -2 upon activation while naïve B cells only reached similar expression levels at later time points in culture. Increased expression of TRAIL-R1 and -2 coincided with a caspase-3-dependent sensitivity to TRAIL-induced apoptosis in activated B cells but not in freshly isolated resting B cells. Finally, both TRAIL-R1 and TRAIL-R2 could signal actively and both contributed to TRAIL-induced apoptosis. In conclusion, this study provides a systematic analysis of the expression of TRAIL-Rs in human primary B cells and of their capacity to signal and induce apoptosis. This dataset forms a basis to further study and understand the dysregulation of TRAIL-Rs and TRAIL expression observed in autoimmune diseases. Additionally, it will be important to foresee potential bystander immunomodulation when TRAIL-R agonists are used in cancer treatment.
Fil: Staniek, Julian. Albert Ludwigs University of Freiburg; Alemania
Fil: Lorenzetti, Raquel. Albert Ludwigs University of Freiburg; Alemania
Fil: Heller, Bianca. Albert Ludwigs University of Freiburg; Alemania
Fil: Janowska, Iga. Albert Ludwigs University of Freiburg; Alemania
Fil: Schneider, Pascal. Universite de Lausanne; Suiza
Fil: Unger, Susanne. Albert Ludwigs University of Freiburg; Alemania
Fil: Warnatz, Klaus. Albert Ludwigs University of Freiburg; Alemania
Fil: Seidl, Maximilian. Albert Ludwigs University of Freiburg; Alemania
Fil: Venhoff, Nils. Albert Ludwigs University of Freiburg; Alemania
Fil: Thiel, Jens. Albert Ludwigs University of Freiburg; Alemania
Fil: Smulski, Cristian Roberto. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina
Fil: Rizzi, Marta. Albert Ludwigs University of Freiburg; Alemania
description The maintenance of B cell homeostasis requires a tight control of B cell generation, survival, activation, and maturation. In lymphocytes upon activation, increased sensitivity to apoptotic signals helps controlling differentiation and proliferation. The death receptor Fas is important in this context because genetic Fas mutations in humans lead to an autoimmune lymphoproliferative syndrome that is similar to lymphoproliferation observed in Fas-deficient mice. In contrast, the physiological role of TNF-related apoptosis-inducing ligand receptors (TRAIL-Rs) in humans has been poorly studied so far. Indeed, most studies have focused on tumor cell lines and on mouse models whose results are difficult to transpose to primary human B cells. In the present work, the expression of apoptosis-inducing TRAIL-R1 and TRAIL-R2 and of the decoy receptors TRAIL-R3 and TRAIL-R4 was systematically studied in all developmental stages of peripheral B cells isolated from the blood and secondary lymphoid organs. Expression of TRAIL-Rs is modulated along development, with highest levels observed in germinal center B cells. In addition, T-dependent and T-independent signals elicited induction of TRAIL-Rs with distinct kinetics, which differed among B cell subpopulations: switched memory cells rapidly upregulated TRAIL-R1 and -2 upon activation while naïve B cells only reached similar expression levels at later time points in culture. Increased expression of TRAIL-R1 and -2 coincided with a caspase-3-dependent sensitivity to TRAIL-induced apoptosis in activated B cells but not in freshly isolated resting B cells. Finally, both TRAIL-R1 and TRAIL-R2 could signal actively and both contributed to TRAIL-induced apoptosis. In conclusion, this study provides a systematic analysis of the expression of TRAIL-Rs in human primary B cells and of their capacity to signal and induce apoptosis. This dataset forms a basis to further study and understand the dysregulation of TRAIL-Rs and TRAIL expression observed in autoimmune diseases. Additionally, it will be important to foresee potential bystander immunomodulation when TRAIL-R agonists are used in cancer treatment.
publishDate 2019
dc.date.none.fl_str_mv 2019-04
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/11336/174901
Staniek, Julian; Lorenzetti, Raquel; Heller, Bianca; Janowska, Iga; Schneider, Pascal; et al.; TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes; Frontiers Media; Frontiers in Immunology; 10; 4-2019; 1-13
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174901
identifier_str_mv Staniek, Julian; Lorenzetti, Raquel; Heller, Bianca; Janowska, Iga; Schneider, Pascal; et al.; TRAIL-R1 and TRAIL-R2 mediate TRAIL-dependent apoptosis in activated primary human B lymphocytes; Frontiers Media; Frontiers in Immunology; 10; 4-2019; 1-13
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2019.00951/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.00951
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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 12.982451

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