Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN
- Autores
- Merlotti Ippólito, Antonela; Dantas, Ezequiel Carlos; Remes Lenicov, Federico; Ceballos, Ana; Jancic, Carolina Cristina; Varese, Augusto; Rubione, Julia; Stover, Juliana Beatriz; Geffner, Jorge Raúl; Sabatte, Juan Atilio
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- STUDY QUESTION: Could seminal plasma clusterin play a role in the uptake of stress-damaged proteins by dendritic cells? SUMMARY ANSWER: Seminal plasma clusterin, but not serum clusterin, promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN. WHAT IS KNOWN ALREADY: Clusterin is one of the major extracellular chaperones. It interacts with a variety of stressed proteins to prevent their aggregation, guiding them for receptor-mediated endocytosis and intracellular degradation. The concentration of clusterin in semen is almost 20-fold higher than that found in serum, raising the question about the role of seminal plasma clusterin in reproduction. No previous studies have analyzed whether seminal plasma clusterin has chaperone activity. We have previously shown that seminal plasma clusterin, but not serum clusterin, expresses an extreme abundance of fucosylated glycans. These motifs enable seminal plasma clusterin to bind DC-SIGN with very high affinity. STUDY DESIGN, SIZE, DURATION: In vitro experiments were performed to evaluate the ability of seminal plasma clusterin to inhibit the precipitation of stressed proteins, promoting their uptake by dendritic cells via DC-SIGN (a C-type lectin receptor selectively expressed on dendritic cells (DC)). Moreover, the ability of seminal plasma clusterin to modulate the phenotype and function of DCs was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clusterin was purified from human semen and human serum. Catalase, bovine serum albumin, glutathione S-transferase, and normal human serum were stressed and the ability of seminal plasma clusterin to prevent the precipitation of these proteins, guiding them to DC-SIGN expressed by DCs, was evaluated using a fluorescence-activated cell sorter (FACS). Endocytosis of stressed proteins was analyzed by confocal microscopy and the ability of seminal plasma clusterin-treated DCs to stimulate the proliferation of CD25+FOXP3+CD4+ T cells was also evaluated by FACS. MAIN RESULTS AND THE ROLE OF CHANCE: Seminal plasma clusterin interacts with stressed proteins, inhibits their aggregation (P < 0.01) and efficiently targets them to dendritic cells via DC-SIGN (P < 0.01). DCs efficiently endocytosed clusterin-client complexes and sorted them to degradative compartments involved in antigen processing and presentation. Moreover, we also found that the interaction of seminal plasma clusterin with DC-SIGN did not change the phenotype of DCs, but stimulates their ability to induce the expansion of CD25+FOXP3+CD4+ T lymphocytes (P < 0.05 versus control). LIMITATIONS, REASONS FOR CAUTION: All the experiments were performed in vitro; hence the relevance of our observations should be validated in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that by inducing the endocytosis of stress-damaged proteins by DCs via DC-SIGN, seminal plasma clusterin might promote a tolerogenic response to male antigens, thereby contributing to female tolerance to seminal antigens. STUDY FUNDING/COMPETING INTEREST(S): The present research was supported by the Consejo Nacional de Investigaciones Científicas y Técnicas, the Buenos Aires University School of Medicine, and the Agencia Nacional de Promoción Científica y Tecnológica (Argentina). The authors have no conflicts of interest to declare.
Fil: Merlotti Ippólito, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Dantas, Ezequiel Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Remes Lenicov, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Ceballos, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Rubione, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Stover, Juliana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Sabatte, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina - Materia
-
Clusterin
Dc-Sign
Dendritic
Semen
Tolerance - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/38139
Ver los metadatos del registro completo
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Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGNMerlotti Ippólito, AntonelaDantas, Ezequiel CarlosRemes Lenicov, FedericoCeballos, AnaJancic, Carolina CristinaVarese, AugustoRubione, JuliaStover, Juliana BeatrizGeffner, Jorge RaúlSabatte, Juan AtilioClusterinDc-SignDendriticSemenTolerancehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3STUDY QUESTION: Could seminal plasma clusterin play a role in the uptake of stress-damaged proteins by dendritic cells? SUMMARY ANSWER: Seminal plasma clusterin, but not serum clusterin, promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN. WHAT IS KNOWN ALREADY: Clusterin is one of the major extracellular chaperones. It interacts with a variety of stressed proteins to prevent their aggregation, guiding them for receptor-mediated endocytosis and intracellular degradation. The concentration of clusterin in semen is almost 20-fold higher than that found in serum, raising the question about the role of seminal plasma clusterin in reproduction. No previous studies have analyzed whether seminal plasma clusterin has chaperone activity. We have previously shown that seminal plasma clusterin, but not serum clusterin, expresses an extreme abundance of fucosylated glycans. These motifs enable seminal plasma clusterin to bind DC-SIGN with very high affinity. STUDY DESIGN, SIZE, DURATION: In vitro experiments were performed to evaluate the ability of seminal plasma clusterin to inhibit the precipitation of stressed proteins, promoting their uptake by dendritic cells via DC-SIGN (a C-type lectin receptor selectively expressed on dendritic cells (DC)). Moreover, the ability of seminal plasma clusterin to modulate the phenotype and function of DCs was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clusterin was purified from human semen and human serum. Catalase, bovine serum albumin, glutathione S-transferase, and normal human serum were stressed and the ability of seminal plasma clusterin to prevent the precipitation of these proteins, guiding them to DC-SIGN expressed by DCs, was evaluated using a fluorescence-activated cell sorter (FACS). Endocytosis of stressed proteins was analyzed by confocal microscopy and the ability of seminal plasma clusterin-treated DCs to stimulate the proliferation of CD25+FOXP3+CD4+ T cells was also evaluated by FACS. MAIN RESULTS AND THE ROLE OF CHANCE: Seminal plasma clusterin interacts with stressed proteins, inhibits their aggregation (P < 0.01) and efficiently targets them to dendritic cells via DC-SIGN (P < 0.01). DCs efficiently endocytosed clusterin-client complexes and sorted them to degradative compartments involved in antigen processing and presentation. Moreover, we also found that the interaction of seminal plasma clusterin with DC-SIGN did not change the phenotype of DCs, but stimulates their ability to induce the expansion of CD25+FOXP3+CD4+ T lymphocytes (P < 0.05 versus control). LIMITATIONS, REASONS FOR CAUTION: All the experiments were performed in vitro; hence the relevance of our observations should be validated in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that by inducing the endocytosis of stress-damaged proteins by DCs via DC-SIGN, seminal plasma clusterin might promote a tolerogenic response to male antigens, thereby contributing to female tolerance to seminal antigens. STUDY FUNDING/COMPETING INTEREST(S): The present research was supported by the Consejo Nacional de Investigaciones Científicas y Técnicas, the Buenos Aires University School of Medicine, and the Agencia Nacional de Promoción Científica y Tecnológica (Argentina). The authors have no conflicts of interest to declare.Fil: Merlotti Ippólito, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Dantas, Ezequiel Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Remes Lenicov, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ceballos, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Rubione, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Stover, Juliana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Sabatte, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaOxford University Press2015-02info: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/pdfhttp://hdl.handle.net/11336/38139Merlotti Ippólito, Antonela; Dantas, Ezequiel Carlos; Remes Lenicov, Federico; Ceballos, Ana; Jancic, Carolina Cristina; et al.; Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN; Oxford University Press; Human Reproduction; 30; 7; 2-2015; 1545-15560268-1161CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/humrep/dev113info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/humrep/article/30/7/1545/653879info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:36Zoai:ri.conicet.gov.ar:11336/38139instacron: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:34982025-09-29 10:15:36.406CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN |
| title |
Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN |
| spellingShingle |
Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN Merlotti Ippólito, Antonela Clusterin Dc-Sign Dendritic Semen Tolerance |
| title_short |
Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN |
| title_full |
Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN |
| title_fullStr |
Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN |
| title_full_unstemmed |
Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN |
| title_sort |
Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN |
| dc.creator.none.fl_str_mv |
Merlotti Ippólito, Antonela Dantas, Ezequiel Carlos Remes Lenicov, Federico Ceballos, Ana Jancic, Carolina Cristina Varese, Augusto Rubione, Julia Stover, Juliana Beatriz Geffner, Jorge Raúl Sabatte, Juan Atilio |
| author |
Merlotti Ippólito, Antonela |
| author_facet |
Merlotti Ippólito, Antonela Dantas, Ezequiel Carlos Remes Lenicov, Federico Ceballos, Ana Jancic, Carolina Cristina Varese, Augusto Rubione, Julia Stover, Juliana Beatriz Geffner, Jorge Raúl Sabatte, Juan Atilio |
| author_role |
author |
| author2 |
Dantas, Ezequiel Carlos Remes Lenicov, Federico Ceballos, Ana Jancic, Carolina Cristina Varese, Augusto Rubione, Julia Stover, Juliana Beatriz Geffner, Jorge Raúl Sabatte, Juan Atilio |
| author2_role |
author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Clusterin Dc-Sign Dendritic Semen Tolerance |
| topic |
Clusterin Dc-Sign Dendritic Semen Tolerance |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
STUDY QUESTION: Could seminal plasma clusterin play a role in the uptake of stress-damaged proteins by dendritic cells? SUMMARY ANSWER: Seminal plasma clusterin, but not serum clusterin, promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN. WHAT IS KNOWN ALREADY: Clusterin is one of the major extracellular chaperones. It interacts with a variety of stressed proteins to prevent their aggregation, guiding them for receptor-mediated endocytosis and intracellular degradation. The concentration of clusterin in semen is almost 20-fold higher than that found in serum, raising the question about the role of seminal plasma clusterin in reproduction. No previous studies have analyzed whether seminal plasma clusterin has chaperone activity. We have previously shown that seminal plasma clusterin, but not serum clusterin, expresses an extreme abundance of fucosylated glycans. These motifs enable seminal plasma clusterin to bind DC-SIGN with very high affinity. STUDY DESIGN, SIZE, DURATION: In vitro experiments were performed to evaluate the ability of seminal plasma clusterin to inhibit the precipitation of stressed proteins, promoting their uptake by dendritic cells via DC-SIGN (a C-type lectin receptor selectively expressed on dendritic cells (DC)). Moreover, the ability of seminal plasma clusterin to modulate the phenotype and function of DCs was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clusterin was purified from human semen and human serum. Catalase, bovine serum albumin, glutathione S-transferase, and normal human serum were stressed and the ability of seminal plasma clusterin to prevent the precipitation of these proteins, guiding them to DC-SIGN expressed by DCs, was evaluated using a fluorescence-activated cell sorter (FACS). Endocytosis of stressed proteins was analyzed by confocal microscopy and the ability of seminal plasma clusterin-treated DCs to stimulate the proliferation of CD25+FOXP3+CD4+ T cells was also evaluated by FACS. MAIN RESULTS AND THE ROLE OF CHANCE: Seminal plasma clusterin interacts with stressed proteins, inhibits their aggregation (P < 0.01) and efficiently targets them to dendritic cells via DC-SIGN (P < 0.01). DCs efficiently endocytosed clusterin-client complexes and sorted them to degradative compartments involved in antigen processing and presentation. Moreover, we also found that the interaction of seminal plasma clusterin with DC-SIGN did not change the phenotype of DCs, but stimulates their ability to induce the expansion of CD25+FOXP3+CD4+ T lymphocytes (P < 0.05 versus control). LIMITATIONS, REASONS FOR CAUTION: All the experiments were performed in vitro; hence the relevance of our observations should be validated in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that by inducing the endocytosis of stress-damaged proteins by DCs via DC-SIGN, seminal plasma clusterin might promote a tolerogenic response to male antigens, thereby contributing to female tolerance to seminal antigens. STUDY FUNDING/COMPETING INTEREST(S): The present research was supported by the Consejo Nacional de Investigaciones Científicas y Técnicas, the Buenos Aires University School of Medicine, and the Agencia Nacional de Promoción Científica y Tecnológica (Argentina). The authors have no conflicts of interest to declare. Fil: Merlotti Ippólito, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Dantas, Ezequiel Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Remes Lenicov, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Ceballos, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Rubione, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Stover, Juliana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Sabatte, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina |
| description |
STUDY QUESTION: Could seminal plasma clusterin play a role in the uptake of stress-damaged proteins by dendritic cells? SUMMARY ANSWER: Seminal plasma clusterin, but not serum clusterin, promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN. WHAT IS KNOWN ALREADY: Clusterin is one of the major extracellular chaperones. It interacts with a variety of stressed proteins to prevent their aggregation, guiding them for receptor-mediated endocytosis and intracellular degradation. The concentration of clusterin in semen is almost 20-fold higher than that found in serum, raising the question about the role of seminal plasma clusterin in reproduction. No previous studies have analyzed whether seminal plasma clusterin has chaperone activity. We have previously shown that seminal plasma clusterin, but not serum clusterin, expresses an extreme abundance of fucosylated glycans. These motifs enable seminal plasma clusterin to bind DC-SIGN with very high affinity. STUDY DESIGN, SIZE, DURATION: In vitro experiments were performed to evaluate the ability of seminal plasma clusterin to inhibit the precipitation of stressed proteins, promoting their uptake by dendritic cells via DC-SIGN (a C-type lectin receptor selectively expressed on dendritic cells (DC)). Moreover, the ability of seminal plasma clusterin to modulate the phenotype and function of DCs was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clusterin was purified from human semen and human serum. Catalase, bovine serum albumin, glutathione S-transferase, and normal human serum were stressed and the ability of seminal plasma clusterin to prevent the precipitation of these proteins, guiding them to DC-SIGN expressed by DCs, was evaluated using a fluorescence-activated cell sorter (FACS). Endocytosis of stressed proteins was analyzed by confocal microscopy and the ability of seminal plasma clusterin-treated DCs to stimulate the proliferation of CD25+FOXP3+CD4+ T cells was also evaluated by FACS. MAIN RESULTS AND THE ROLE OF CHANCE: Seminal plasma clusterin interacts with stressed proteins, inhibits their aggregation (P < 0.01) and efficiently targets them to dendritic cells via DC-SIGN (P < 0.01). DCs efficiently endocytosed clusterin-client complexes and sorted them to degradative compartments involved in antigen processing and presentation. Moreover, we also found that the interaction of seminal plasma clusterin with DC-SIGN did not change the phenotype of DCs, but stimulates their ability to induce the expansion of CD25+FOXP3+CD4+ T lymphocytes (P < 0.05 versus control). LIMITATIONS, REASONS FOR CAUTION: All the experiments were performed in vitro; hence the relevance of our observations should be validated in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that by inducing the endocytosis of stress-damaged proteins by DCs via DC-SIGN, seminal plasma clusterin might promote a tolerogenic response to male antigens, thereby contributing to female tolerance to seminal antigens. STUDY FUNDING/COMPETING INTEREST(S): The present research was supported by the Consejo Nacional de Investigaciones Científicas y Técnicas, the Buenos Aires University School of Medicine, and the Agencia Nacional de Promoción Científica y Tecnológica (Argentina). The authors have no conflicts of interest to declare. |
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2015 |
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http://hdl.handle.net/11336/38139 Merlotti Ippólito, Antonela; Dantas, Ezequiel Carlos; Remes Lenicov, Federico; Ceballos, Ana; Jancic, Carolina Cristina; et al.; Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN; Oxford University Press; Human Reproduction; 30; 7; 2-2015; 1545-1556 0268-1161 CONICET Digital CONICET |
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Merlotti Ippólito, Antonela; Dantas, Ezequiel Carlos; Remes Lenicov, Federico; Ceballos, Ana; Jancic, Carolina Cristina; et al.; Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN; Oxford University Press; Human Reproduction; 30; 7; 2-2015; 1545-1556 0268-1161 CONICET Digital CONICET |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1093/humrep/dev113 info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/humrep/article/30/7/1545/653879 |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1844614093137248256 |
| score |
13.069144 |