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

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 c...

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Autores principales:	Caldirola, M.S., Broggi, M.G.R., Gaillard, M.I., Bezrodnik, L., Zwirner, N.W.
Formato:	JOUR
Materias:	CD25 IL-2 Natural killer cells Primary immunodeficiencies STAT5b CD16 antigen CD3 antigen CD56 antigen chemokine receptor CCR7 gamma interferon granzyme B interleukin 15 interleukin 2 interleukin 2 receptor alpha L selectin monoclonal antibody nerve cell adhesion molecule perforin STAT5b protein Article atopic dermatitis autoimmune thyroiditis case report cell count cell maturation cell proliferation assay chronic diarrhea clinical article controlled study cytokine production degranulation assay down regulation eczema female flow cytometry growth disorder human human cell immune deficiency immunohistochemistry lower respiratory tract infection natural killer cell peripheral blood mononuclear cell phenotype pneumonia protein expression signal transduction upregulation
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_16643224_v9_nJUN_p_Caldirola
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_16643224_v9_nJUN_p_Caldirola2023-10-03T16:29:08Z Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation Caldirola, M.S. Broggi, M.G.R. Gaillard, M.I. Bezrodnik, L. Zwirner, N.W. CD25 IL-2 Natural killer cells Primary immunodeficiencies STAT5b CD16 antigen CD3 antigen CD56 antigen chemokine receptor CCR7 gamma interferon granzyme B interleukin 15 interleukin 2 interleukin 2 receptor alpha L selectin monoclonal antibody nerve cell adhesion molecule perforin STAT5b protein Article atopic dermatitis autoimmune thyroiditis case report cell count cell maturation cell proliferation assay chronic diarrhea clinical article controlled study cytokine production degranulation assay down regulation eczema female flow cytometry growth disorder human human cell immune deficiency immunohistochemistry lower respiratory tract infection natural killer cell peripheral blood mononuclear cell phenotype pneumonia protein expression signal transduction upregulation 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. © 2018 Caldirola, Rodríguez Broggi, Gaillard, Bezrodnik and Zwirner. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_16643224_v9_nJUN_p_Caldirola
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	CD25 IL-2 Natural killer cells Primary immunodeficiencies STAT5b CD16 antigen CD3 antigen CD56 antigen chemokine receptor CCR7 gamma interferon granzyme B interleukin 15 interleukin 2 interleukin 2 receptor alpha L selectin monoclonal antibody nerve cell adhesion molecule perforin STAT5b protein Article atopic dermatitis autoimmune thyroiditis case report cell count cell maturation cell proliferation assay chronic diarrhea clinical article controlled study cytokine production degranulation assay down regulation eczema female flow cytometry growth disorder human human cell immune deficiency immunohistochemistry lower respiratory tract infection natural killer cell peripheral blood mononuclear cell phenotype pneumonia protein expression signal transduction upregulation
spellingShingle	CD25 IL-2 Natural killer cells Primary immunodeficiencies STAT5b CD16 antigen CD3 antigen CD56 antigen chemokine receptor CCR7 gamma interferon granzyme B interleukin 15 interleukin 2 interleukin 2 receptor alpha L selectin monoclonal antibody nerve cell adhesion molecule perforin STAT5b protein Article atopic dermatitis autoimmune thyroiditis case report cell count cell maturation cell proliferation assay chronic diarrhea clinical article controlled study cytokine production degranulation assay down regulation eczema female flow cytometry growth disorder human human cell immune deficiency immunohistochemistry lower respiratory tract infection natural killer cell peripheral blood mononuclear cell phenotype pneumonia protein expression signal transduction upregulation Caldirola, M.S. Broggi, M.G.R. Gaillard, M.I. Bezrodnik, L. Zwirner, N.W. Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
topic_facet	CD25 IL-2 Natural killer cells Primary immunodeficiencies STAT5b CD16 antigen CD3 antigen CD56 antigen chemokine receptor CCR7 gamma interferon granzyme B interleukin 15 interleukin 2 interleukin 2 receptor alpha L selectin monoclonal antibody nerve cell adhesion molecule perforin STAT5b protein Article atopic dermatitis autoimmune thyroiditis case report cell count cell maturation cell proliferation assay chronic diarrhea clinical article controlled study cytokine production degranulation assay down regulation eczema female flow cytometry growth disorder human human cell immune deficiency immunohistochemistry lower respiratory tract infection natural killer cell peripheral blood mononuclear cell phenotype pneumonia protein expression signal transduction upregulation
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. © 2018 Caldirola, Rodríguez Broggi, Gaillard, Bezrodnik and Zwirner.
format	JOUR
author	Caldirola, M.S. Broggi, M.G.R. Gaillard, M.I. Bezrodnik, L. Zwirner, N.W.
author_facet	Caldirola, M.S. Broggi, M.G.R. Gaillard, M.I. Bezrodnik, L. Zwirner, N.W.
author_sort	Caldirola, M.S.
title	Primary immunodeficiencies unravel the role of IL-2/CD25/STAT5b in human natural killer cell maturation
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
url	http://hdl.handle.net/20.500.12110/paper_16643224_v9_nJUN_p_Caldirola
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_version_	1782025606592987136

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

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