Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation

Autores
Caldirola, Maria Soledad; Rodriguez Broggi, Maria Guadalupe; Gaillard, María Isabel; Bezrodnik, Liliana; Zwirner, Norberto Walter
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Natural killer (NK) cells play a pivotal role during immunity against viruses and circumstantial evidence also indicates that they can protect the host against developing tumors. Peripheral blood NK cells comprise CD56brightCD16lo/- cells that constitutively express CD25 (IL-2Ra) and CD56dimCD16hi cells that express CD25 upon activation. Using NK cells from two patients, one with a primary immunodeficiency characterized by a homozygous mutation in CD25 (born in year 2007 and studied since she was 3 years old) and one with a homozygous mutation in STAT5b (born in year 1992 and studied since she was 10 years old), we observed that the absence of IL-2 signaling through CD25 promotes the accumulation of CD56brightCD16high NK cells, and that CD56brightCD16lo, CD56brightCD16high, and CD56dimCD16high NK cells of this patient exhibited higher content of perforin and granzyme B, and proliferation capacity, compared to healthy donors. Also, CD56bright and CD56dim NK cells of this patient exhibited a reduced IFN-γ production in response to cytokine stimulation and increased degranulation against K562 cells. Also, the CD25-deficient patient presented a lower frequency of terminally differentiated NK cells in the CD56dimCD16hi NK subpopulation compared to the HD (assessed by CD57 and CD94 expression). Remarkably, CD56dimCD16high NK cells from both patients exhibited notoriously higher expression of CD62L compared to HD, suggesting that in the absence of IL-2 signaling through CD25 and STAT5b, NK cells fail to properly downregulate CD62L during their transition from CD56brightCD16lo/- to CD56dimCD16hi cells. Thus, we provide the first demonstration about the in vivo requirement of the integrity of the IL-2/CD25/STAT5b axis for proper human NK cell maturation.
Fil: Caldirola, Maria Soledad. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Fil: Rodriguez Broggi, Maria Guadalupe. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; Argentina
Fil: Gaillard, María Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; Argentina
Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; Argentina. Centro de Inmunología Clínica “Dra. Bezrodnik”; Argentina
Fil: Zwirner, Norberto Walter. 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. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Materia
CD25
IL-2
NATURAL KILLER CELLS
PRIMARY IMMUNODEFICIENCIES
STAT5B
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:11336/91056
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/91056
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturationCaldirola, Maria SoledadRodriguez Broggi, Maria GuadalupeGaillard, María IsabelBezrodnik, LilianaZwirner, Norberto WalterCD25IL-2NATURAL KILLER CELLSPRIMARY IMMUNODEFICIENCIESSTAT5Bhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Natural killer (NK) cells play a pivotal role during immunity against viruses and circumstantial evidence also indicates that they can protect the host against developing tumors. Peripheral blood NK cells comprise CD56brightCD16lo/- cells that constitutively express CD25 (IL-2Ra) and CD56dimCD16hi cells that express CD25 upon activation. Using NK cells from two patients, one with a primary immunodeficiency characterized by a homozygous mutation in CD25 (born in year 2007 and studied since she was 3 years old) and one with a homozygous mutation in STAT5b (born in year 1992 and studied since she was 10 years old), we observed that the absence of IL-2 signaling through CD25 promotes the accumulation of CD56brightCD16high NK cells, and that CD56brightCD16lo, CD56brightCD16high, and CD56dimCD16high NK cells of this patient exhibited higher content of perforin and granzyme B, and proliferation capacity, compared to healthy donors. Also, CD56bright and CD56dim NK cells of this patient exhibited a reduced IFN-γ production in response to cytokine stimulation and increased degranulation against K562 cells. Also, the CD25-deficient patient presented a lower frequency of terminally differentiated NK cells in the CD56dimCD16hi NK subpopulation compared to the HD (assessed by CD57 and CD94 expression). Remarkably, CD56dimCD16high NK cells from both patients exhibited notoriously higher expression of CD62L compared to HD, suggesting that in the absence of IL-2 signaling through CD25 and STAT5b, NK cells fail to properly downregulate CD62L during their transition from CD56brightCD16lo/- to CD56dimCD16hi cells. Thus, we provide the first demonstration about the in vivo requirement of the integrity of the IL-2/CD25/STAT5b axis for proper human NK cell maturation.Fil: Caldirola, Maria Soledad. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Rodriguez Broggi, Maria Guadalupe. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; ArgentinaFil: Gaillard, María Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; ArgentinaFil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; Argentina. Centro de Inmunología Clínica “Dra. Bezrodnik”; ArgentinaFil: Zwirner, Norberto Walter. 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. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; ArgentinaFrontiers Media S.A.2018-06-22info: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/11336/91056Caldirola, Maria Soledad; Rodriguez Broggi, Maria Guadalupe; Gaillard, María Isabel; Bezrodnik, Liliana; Zwirner, Norberto Walter; Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation; Frontiers Media S.A.; Frontiers in Immunology; 9; 22-6-2018; 1429-14291664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2018.01429/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.01429info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:09Zoai:ri.conicet.gov.ar:11336/91056instacron: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:34982025-09-03 09:58:09.327CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
title Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
spellingShingle Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
Caldirola, Maria Soledad
CD25
IL-2
NATURAL KILLER CELLS
PRIMARY IMMUNODEFICIENCIES
STAT5B
title_short Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
title_full Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
title_fullStr Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
title_full_unstemmed Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
title_sort Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
dc.creator.none.fl_str_mv Caldirola, Maria Soledad
Rodriguez Broggi, Maria Guadalupe
Gaillard, María Isabel
Bezrodnik, Liliana
Zwirner, Norberto Walter
author Caldirola, Maria Soledad
author_facet Caldirola, Maria Soledad
Rodriguez Broggi, Maria Guadalupe
Gaillard, María Isabel
Bezrodnik, Liliana
Zwirner, Norberto Walter
author_role author
author2 Rodriguez Broggi, Maria Guadalupe
Gaillard, María Isabel
Bezrodnik, Liliana
Zwirner, Norberto Walter
author2_role author
author
author
author
dc.subject.none.fl_str_mv CD25
IL-2
NATURAL KILLER CELLS
PRIMARY IMMUNODEFICIENCIES
STAT5B
topic CD25
IL-2
NATURAL KILLER CELLS
PRIMARY IMMUNODEFICIENCIES
STAT5B
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Natural killer (NK) cells play a pivotal role during immunity against viruses and circumstantial evidence also indicates that they can protect the host against developing tumors. Peripheral blood NK cells comprise CD56brightCD16lo/- cells that constitutively express CD25 (IL-2Ra) and CD56dimCD16hi cells that express CD25 upon activation. Using NK cells from two patients, one with a primary immunodeficiency characterized by a homozygous mutation in CD25 (born in year 2007 and studied since she was 3 years old) and one with a homozygous mutation in STAT5b (born in year 1992 and studied since she was 10 years old), we observed that the absence of IL-2 signaling through CD25 promotes the accumulation of CD56brightCD16high NK cells, and that CD56brightCD16lo, CD56brightCD16high, and CD56dimCD16high NK cells of this patient exhibited higher content of perforin and granzyme B, and proliferation capacity, compared to healthy donors. Also, CD56bright and CD56dim NK cells of this patient exhibited a reduced IFN-γ production in response to cytokine stimulation and increased degranulation against K562 cells. Also, the CD25-deficient patient presented a lower frequency of terminally differentiated NK cells in the CD56dimCD16hi NK subpopulation compared to the HD (assessed by CD57 and CD94 expression). Remarkably, CD56dimCD16high NK cells from both patients exhibited notoriously higher expression of CD62L compared to HD, suggesting that in the absence of IL-2 signaling through CD25 and STAT5b, NK cells fail to properly downregulate CD62L during their transition from CD56brightCD16lo/- to CD56dimCD16hi cells. Thus, we provide the first demonstration about the in vivo requirement of the integrity of the IL-2/CD25/STAT5b axis for proper human NK cell maturation.
Fil: Caldirola, Maria Soledad. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Fil: Rodriguez Broggi, Maria Guadalupe. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; Argentina
Fil: Gaillard, María Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; Argentina
Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Area de Inmunología. Grupo de Inmunología; Argentina. Centro de Inmunología Clínica “Dra. Bezrodnik”; Argentina
Fil: Zwirner, Norberto Walter. 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. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
description Natural killer (NK) cells play a pivotal role during immunity against viruses and circumstantial evidence also indicates that they can protect the host against developing tumors. Peripheral blood NK cells comprise CD56brightCD16lo/- cells that constitutively express CD25 (IL-2Ra) and CD56dimCD16hi cells that express CD25 upon activation. Using NK cells from two patients, one with a primary immunodeficiency characterized by a homozygous mutation in CD25 (born in year 2007 and studied since she was 3 years old) and one with a homozygous mutation in STAT5b (born in year 1992 and studied since she was 10 years old), we observed that the absence of IL-2 signaling through CD25 promotes the accumulation of CD56brightCD16high NK cells, and that CD56brightCD16lo, CD56brightCD16high, and CD56dimCD16high NK cells of this patient exhibited higher content of perforin and granzyme B, and proliferation capacity, compared to healthy donors. Also, CD56bright and CD56dim NK cells of this patient exhibited a reduced IFN-γ production in response to cytokine stimulation and increased degranulation against K562 cells. Also, the CD25-deficient patient presented a lower frequency of terminally differentiated NK cells in the CD56dimCD16hi NK subpopulation compared to the HD (assessed by CD57 and CD94 expression). Remarkably, CD56dimCD16high NK cells from both patients exhibited notoriously higher expression of CD62L compared to HD, suggesting that in the absence of IL-2 signaling through CD25 and STAT5b, NK cells fail to properly downregulate CD62L during their transition from CD56brightCD16lo/- to CD56dimCD16hi cells. Thus, we provide the first demonstration about the in vivo requirement of the integrity of the IL-2/CD25/STAT5b axis for proper human NK cell maturation.
publishDate 2018
dc.date.none.fl_str_mv 2018-06-22
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/11336/91056
Caldirola, Maria Soledad; Rodriguez Broggi, Maria Guadalupe; Gaillard, María Isabel; Bezrodnik, Liliana; Zwirner, Norberto Walter; Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation; Frontiers Media S.A.; Frontiers in Immunology; 9; 22-6-2018; 1429-1429
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/91056
identifier_str_mv Caldirola, Maria Soledad; Rodriguez Broggi, Maria Guadalupe; Gaillard, María Isabel; Bezrodnik, Liliana; Zwirner, Norberto Walter; Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation; Frontiers Media S.A.; Frontiers in Immunology; 9; 22-6-2018; 1429-1429
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/articles/10.3389/fimmu.2018.01429/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.01429
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
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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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