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01-10-2021 | Original Article

Phenotypes of STAT3 gain-of-function variant related to disruptive regulation of CXCL8/STAT3, KIT/STAT3, and IL-2/CD25/Treg axes

Authors: Lia Furlaneto Marega, Janine Schincariol Sabino, Marcus Vinicius Pedroni, Marcelo Teocchi, Carolina Lanaro, Dulcinéia Martins de Albuquerque, Irene Pereira dos Santos, Fernando Ferreira Costa, Maria Marluce dos Santos Vilela

Published in: Immunologic Research | Issue 5/2021

Abstract

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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Title: Phenotypes of STAT3 gain-of-function variant related to disruptive regulation of CXCL8/STAT3, KIT/STAT3, and IL-2/CD25/Treg axes
Authors: Lia Furlaneto Marega
Janine Schincariol Sabino
Marcus Vinicius Pedroni
Marcelo Teocchi
Carolina Lanaro
Dulcinéia Martins de Albuquerque
Irene Pereira dos Santos
Fernando Ferreira Costa
Maria Marluce dos Santos Vilela
Publication date: 01-10-2021
Publisher: Springer US
Published in: Immunologic Research / Issue 5/2021
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-021-09225-0

At a glance: The ONWARDS insulin icodec trials

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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

Abstract

At a glance: The ONWARDS insulin icodec trials

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