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The STAT5b Pathway Defect and Autoimmunity

The signal transducer and activator of transcription (STAT) 5b is a universal transcription factor that plays key biological roles in allergic diseases, immunodeficiencies, autoimmunities, cancers, hematological diseases, growth disorders, and lung diseases. The identification of distinct pathologic...

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Autores principales: Kanai, Takahiro, Jenks, Jennifer, Nadeau, Kari Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418548/
https://www.ncbi.nlm.nih.gov/pubmed/22912632
http://dx.doi.org/10.3389/fimmu.2012.00234
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author Kanai, Takahiro
Jenks, Jennifer
Nadeau, Kari Christine
author_facet Kanai, Takahiro
Jenks, Jennifer
Nadeau, Kari Christine
author_sort Kanai, Takahiro
collection PubMed
description The signal transducer and activator of transcription (STAT) 5b is a universal transcription factor that plays key biological roles in allergic diseases, immunodeficiencies, autoimmunities, cancers, hematological diseases, growth disorders, and lung diseases. The identification of distinct pathological manifestations of STAT5b deficiency in humans has highlighted the critical role of the STAT5b pathway. Proper gene transcription at IL-2R α, FOXP3, Bcl-2, and growth hormone (GH) associated loci are thought to be associated with normal STAT5b transcriptional activity. These genes are thought to play important roles in allergy/autoimmunity, immunodeficiency, cancer/anemia, and growth, respectively. The STAT5A and STAT5B genes are collocated on 17q11. Although these two monomeric proteins exhibit peptide sequence similarities of >90%, it is known through observations of STAT5b deficient subjects that STAT5a and STAT5b are not fully redundant in humans. Patients with STAT5b deficiency have decreased numbers of regulatory CD4(+)CD25(high) T cell (Treg) despite their STAT5a levels being normal. Prior studies on STAT5b deficient subjects have revealed immunological aberrations associated with the following disease phenotype: modest lymphopenia and decreased populations of Treg, γ−δ T cells, and natural killer (NK) cells. Most subjects with STAT5b deficiency show severe eczema, and autoimmune disease (juvenile idiopathic arthritis, autoimmune thyroiditis, idiopathic thrombocytic purpura) which are thought to be associated with Treg dysfunction. We will review the likely pathophysiological mechanisms associated with STAT5b deficiency.
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spelling pubmed-34185482012-08-21 The STAT5b Pathway Defect and Autoimmunity Kanai, Takahiro Jenks, Jennifer Nadeau, Kari Christine Front Immunol Immunology The signal transducer and activator of transcription (STAT) 5b is a universal transcription factor that plays key biological roles in allergic diseases, immunodeficiencies, autoimmunities, cancers, hematological diseases, growth disorders, and lung diseases. The identification of distinct pathological manifestations of STAT5b deficiency in humans has highlighted the critical role of the STAT5b pathway. Proper gene transcription at IL-2R α, FOXP3, Bcl-2, and growth hormone (GH) associated loci are thought to be associated with normal STAT5b transcriptional activity. These genes are thought to play important roles in allergy/autoimmunity, immunodeficiency, cancer/anemia, and growth, respectively. The STAT5A and STAT5B genes are collocated on 17q11. Although these two monomeric proteins exhibit peptide sequence similarities of >90%, it is known through observations of STAT5b deficient subjects that STAT5a and STAT5b are not fully redundant in humans. Patients with STAT5b deficiency have decreased numbers of regulatory CD4(+)CD25(high) T cell (Treg) despite their STAT5a levels being normal. Prior studies on STAT5b deficient subjects have revealed immunological aberrations associated with the following disease phenotype: modest lymphopenia and decreased populations of Treg, γ−δ T cells, and natural killer (NK) cells. Most subjects with STAT5b deficiency show severe eczema, and autoimmune disease (juvenile idiopathic arthritis, autoimmune thyroiditis, idiopathic thrombocytic purpura) which are thought to be associated with Treg dysfunction. We will review the likely pathophysiological mechanisms associated with STAT5b deficiency. Frontiers Research Foundation 2012-08-14 /pmc/articles/PMC3418548/ /pubmed/22912632 http://dx.doi.org/10.3389/fimmu.2012.00234 Text en Copyright © 2012 Kanai, Jenks and Nadeau. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Immunology
Kanai, Takahiro
Jenks, Jennifer
Nadeau, Kari Christine
The STAT5b Pathway Defect and Autoimmunity
title The STAT5b Pathway Defect and Autoimmunity
title_full The STAT5b Pathway Defect and Autoimmunity
title_fullStr The STAT5b Pathway Defect and Autoimmunity
title_full_unstemmed The STAT5b Pathway Defect and Autoimmunity
title_short The STAT5b Pathway Defect and Autoimmunity
title_sort stat5b pathway defect and autoimmunity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418548/
https://www.ncbi.nlm.nih.gov/pubmed/22912632
http://dx.doi.org/10.3389/fimmu.2012.00234
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