GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection

Autores
Ortiz Wilczyñski, Juan Manuel; Olexen, Cinthia Mariel; Errasti, Andrea Emilse; Schattner, Mirta Ana; Rothlin, Carla; Correale, Jorge; Carrera Silva, Eugenio Antonio
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Multiple sclerosis (MS) is a highly disabling neurodegenerative autoimmune condition in which an unbalanced immune response plays a critical role. Although the mechanisms remain poorly defined, helminth infections are known to modulate the severity and progression of chronic inflammatory diseases. The tyrosine kinase receptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immune response in various inflammatory settings. We show here that patients with concurrent natural helminth infections and MS condition (HIMS) had an increased expression of the negative regulatory TAM receptors in antigen-presenting cells and their agonist GAS6 in circulating CD11bhigh and CD4+ T cells compared to patients with only MS. The Th17 subset was reduced in patients with HIMS with a subsequent downregulation of its pathogenic genetic program. Moreover, these CD4+ T cells promoted lower levels of the co-stimulatory molecules CD80, CD86, and CD40 on dendritic cells compared with CD4+ T cells from patients with MS, an effect that was GAS6-dependent. IL-10+ cells from patients with HIMS showed higher GAS6 expression levels than Th17 cells, and inhibition of phosphatidylserine/GAS6 binding led to an expansion of Th17 effector genes. The addition of GAS6 on activated CD4+ T cells from patients with MS restrains the Th17 gene expression signature. This cohort of patients with HIMS unravels a promising regulatory mechanism to dampen the Th17 inflammatory response in autoimmunity.
Fil: Ortiz Wilczyñski, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Olexen, Cinthia Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rothlin, Carla. University of Yale; Estados Unidos
Fil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
MULTIPLE SCLEROSIS
HELMINTHS INFECTION
TAM RECEPTORS
GAS6
Th17 GENE EXPRESSION SIGNATURE
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:11336/146354
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/146354
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infectionOrtiz Wilczyñski, Juan ManuelOlexen, Cinthia MarielErrasti, Andrea EmilseSchattner, Mirta AnaRothlin, CarlaCorreale, JorgeCarrera Silva, Eugenio AntonioMULTIPLE SCLEROSISHELMINTHS INFECTIONTAM RECEPTORSGAS6Th17 GENE EXPRESSION SIGNATUREhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Multiple sclerosis (MS) is a highly disabling neurodegenerative autoimmune condition in which an unbalanced immune response plays a critical role. Although the mechanisms remain poorly defined, helminth infections are known to modulate the severity and progression of chronic inflammatory diseases. The tyrosine kinase receptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immune response in various inflammatory settings. We show here that patients with concurrent natural helminth infections and MS condition (HIMS) had an increased expression of the negative regulatory TAM receptors in antigen-presenting cells and their agonist GAS6 in circulating CD11bhigh and CD4+ T cells compared to patients with only MS. The Th17 subset was reduced in patients with HIMS with a subsequent downregulation of its pathogenic genetic program. Moreover, these CD4+ T cells promoted lower levels of the co-stimulatory molecules CD80, CD86, and CD40 on dendritic cells compared with CD4+ T cells from patients with MS, an effect that was GAS6-dependent. IL-10+ cells from patients with HIMS showed higher GAS6 expression levels than Th17 cells, and inhibition of phosphatidylserine/GAS6 binding led to an expansion of Th17 effector genes. The addition of GAS6 on activated CD4+ T cells from patients with MS restrains the Th17 gene expression signature. This cohort of patients with HIMS unravels a promising regulatory mechanism to dampen the Th17 inflammatory response in autoimmunity.Fil: Ortiz Wilczyñski, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Olexen, Cinthia Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rothlin, Carla. University of Yale; Estados UnidosFil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaPublic Library of Science2020-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/146354Ortiz Wilczyñski, Juan Manuel; Olexen, Cinthia Mariel; Errasti, Andrea Emilse; Schattner, Mirta Ana; Rothlin, Carla; et al.; GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection; Public Library of Science; Plos Pathogens; 16; 12; 12-2020; 1-221553-7366CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009176info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1009176info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-04-08T10:57:29Zoai:ri.conicet.gov.ar:11336/146354instacron: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:34982026-04-08 10:57:29.465CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection
title GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection
spellingShingle GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection
Ortiz Wilczyñski, Juan Manuel
MULTIPLE SCLEROSIS
HELMINTHS INFECTION
TAM RECEPTORS
GAS6
Th17 GENE EXPRESSION SIGNATURE
title_short GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection
title_full GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection
title_fullStr GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection
title_full_unstemmed GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection
title_sort GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection
dc.creator.none.fl_str_mv Ortiz Wilczyñski, Juan Manuel
Olexen, Cinthia Mariel
Errasti, Andrea Emilse
Schattner, Mirta Ana
Rothlin, Carla
Correale, Jorge
Carrera Silva, Eugenio Antonio
author Ortiz Wilczyñski, Juan Manuel
author_facet Ortiz Wilczyñski, Juan Manuel
Olexen, Cinthia Mariel
Errasti, Andrea Emilse
Schattner, Mirta Ana
Rothlin, Carla
Correale, Jorge
Carrera Silva, Eugenio Antonio
author_role author
author2 Olexen, Cinthia Mariel
Errasti, Andrea Emilse
Schattner, Mirta Ana
Rothlin, Carla
Correale, Jorge
Carrera Silva, Eugenio Antonio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv MULTIPLE SCLEROSIS
HELMINTHS INFECTION
TAM RECEPTORS
GAS6
Th17 GENE EXPRESSION SIGNATURE
topic MULTIPLE SCLEROSIS
HELMINTHS INFECTION
TAM RECEPTORS
GAS6
Th17 GENE EXPRESSION SIGNATURE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Multiple sclerosis (MS) is a highly disabling neurodegenerative autoimmune condition in which an unbalanced immune response plays a critical role. Although the mechanisms remain poorly defined, helminth infections are known to modulate the severity and progression of chronic inflammatory diseases. The tyrosine kinase receptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immune response in various inflammatory settings. We show here that patients with concurrent natural helminth infections and MS condition (HIMS) had an increased expression of the negative regulatory TAM receptors in antigen-presenting cells and their agonist GAS6 in circulating CD11bhigh and CD4+ T cells compared to patients with only MS. The Th17 subset was reduced in patients with HIMS with a subsequent downregulation of its pathogenic genetic program. Moreover, these CD4+ T cells promoted lower levels of the co-stimulatory molecules CD80, CD86, and CD40 on dendritic cells compared with CD4+ T cells from patients with MS, an effect that was GAS6-dependent. IL-10+ cells from patients with HIMS showed higher GAS6 expression levels than Th17 cells, and inhibition of phosphatidylserine/GAS6 binding led to an expansion of Th17 effector genes. The addition of GAS6 on activated CD4+ T cells from patients with MS restrains the Th17 gene expression signature. This cohort of patients with HIMS unravels a promising regulatory mechanism to dampen the Th17 inflammatory response in autoimmunity.
Fil: Ortiz Wilczyñski, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Olexen, Cinthia Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rothlin, Carla. University of Yale; Estados Unidos
Fil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Multiple sclerosis (MS) is a highly disabling neurodegenerative autoimmune condition in which an unbalanced immune response plays a critical role. Although the mechanisms remain poorly defined, helminth infections are known to modulate the severity and progression of chronic inflammatory diseases. The tyrosine kinase receptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immune response in various inflammatory settings. We show here that patients with concurrent natural helminth infections and MS condition (HIMS) had an increased expression of the negative regulatory TAM receptors in antigen-presenting cells and their agonist GAS6 in circulating CD11bhigh and CD4+ T cells compared to patients with only MS. The Th17 subset was reduced in patients with HIMS with a subsequent downregulation of its pathogenic genetic program. Moreover, these CD4+ T cells promoted lower levels of the co-stimulatory molecules CD80, CD86, and CD40 on dendritic cells compared with CD4+ T cells from patients with MS, an effect that was GAS6-dependent. IL-10+ cells from patients with HIMS showed higher GAS6 expression levels than Th17 cells, and inhibition of phosphatidylserine/GAS6 binding led to an expansion of Th17 effector genes. The addition of GAS6 on activated CD4+ T cells from patients with MS restrains the Th17 gene expression signature. This cohort of patients with HIMS unravels a promising regulatory mechanism to dampen the Th17 inflammatory response in autoimmunity.
publishDate 2020
dc.date.none.fl_str_mv 2020-12
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/11336/146354
Ortiz Wilczyñski, Juan Manuel; Olexen, Cinthia Mariel; Errasti, Andrea Emilse; Schattner, Mirta Ana; Rothlin, Carla; et al.; GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection; Public Library of Science; Plos Pathogens; 16; 12; 12-2020; 1-22
1553-7366
CONICET Digital
CONICET
url http://hdl.handle.net/11336/146354
identifier_str_mv Ortiz Wilczyñski, Juan Manuel; Olexen, Cinthia Mariel; Errasti, Andrea Emilse; Schattner, Mirta Ana; Rothlin, Carla; et al.; GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection; Public Library of Science; Plos Pathogens; 16; 12; 12-2020; 1-22
1553-7366
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://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009176
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1009176
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
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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 13.018236

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