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Phenotypes of STAT3 gain-of-function variant related to disruptive regulation of CXCL8/STAT3, KIT/STAT3, and IL-2/CD25/Treg axes.
Marega, Lia Furlaneto; Sabino, Janine Schincariol; Pedroni, Marcus Vinicius; Teocchi, Marcelo; Lanaro, Carolina; de Albuquerque, Dulcinéia Martins; Dos Santos, Irene Pereira; Costa, Fernando Ferreira; Dos Santos Vilela, Maria Marluce.
Afiliação
  • Marega LF; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, School of Medical Sciences, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", São Paulo, CEP 13083-887, Campinas, Brazil.
  • Sabino JS; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, School of Medical Sciences, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", São Paulo, CEP 13083-887, Campinas, Brazil.
  • Pedroni MV; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, School of Medical Sciences, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", São Paulo, CEP 13083-887, Campinas, Brazil.
  • Teocchi M; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, School of Medical Sciences, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", São Paulo, CEP 13083-887, Campinas, Brazil.
  • Lanaro C; Hematology and Hemotherapy Center - Hemocentro Campinas, University of Campinas (UNICAMP), SP, Campinas, Brazil.
  • de Albuquerque DM; Hematology and Hemotherapy Center - Hemocentro Campinas, University of Campinas (UNICAMP), SP, Campinas, Brazil.
  • Dos Santos IP; Flow Cytometry Laboratory, Hematology and Hemotherapy Center, University of Campinas (UNICAMP), SP, Campinas, Brazil.
  • Costa FF; Hematology and Hemotherapy Center - Hemocentro Campinas, University of Campinas (UNICAMP), SP, Campinas, Brazil.
  • Dos Santos Vilela MM; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, School of Medical Sciences, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", São Paulo, CEP 13083-887, Campinas, Brazil. marluce@unicamp.br.
Immunol Res ; 69(5): 445-456, 2021 10.
Article em En | MEDLINE | ID: mdl-34390446
STAT3 is a cytokine-signaling transcription factor critical for gene regulation. Gain-of-function (GOF) mutations in STAT3 are associated with lymphoproliferation, autoimmune cytopenias, increased susceptibility to infection, early-onset solid-organ autoimmunity, short stature, and eczema. We studied the JAK/STAT signaling pathway gene expression and the cytokine profile in two families carrying STAT3-GOF variants to shed light on the STAT3-GOF-associated variable expressivity, including the identification of disease markers. Considering 92 target genes, KIT and IL2RA were downregulated only in patients with high clinical penetrance, while CXCL8 was markedly downregulated for all of them. Unlike previous studies, SOCS3-a STAT3 inhibitor-was not upregulated in patients. In addition, low levels of IL-2 and a reduced numbers of Tregs cells were strikingly prevalent in patients. This study shows a disruptive role of STAT3-GOF variants in the regulatory axis activities CXCL8/STAT3, KIT/STAT3, IL2/CD25/Treg, which, by slightly different mechanisms, underlie the broad clinical spectrum seen in the studied patients. In addition, we suggest the investigation of CXCL8 as a biomarker for identifying STAT3-GOF mutation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-8 / Interleucina-2 / Linfócitos T Reguladores / Fator de Transcrição STAT3 / Subunidade alfa de Receptor de Interleucina-2 / Mutação com Ganho de Função Tipo de estudo: Prognostic_studies Limite: Adult / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Immunol Res Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-8 / Interleucina-2 / Linfócitos T Reguladores / Fator de Transcrição STAT3 / Subunidade alfa de Receptor de Interleucina-2 / Mutação com Ganho de Função Tipo de estudo: Prognostic_studies Limite: Adult / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Immunol Res Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos