De novo mutations promote inflammation in children with STAT3 gain-of-function syndrome by affecting IL-1β expression.

Autor: Chen JY; Department of Nephrology & Rheumatology, Kunming Children's Hospital, Kunming 650228, Yunnan, China., Li YF; Department of Nephrology & Rheumatology, Kunming Children's Hospital, Kunming 650228, Yunnan, China., Zhou Z; Department of Nephrology, First Affiliated Hospital of Kunming Medical University, Yunnan Clinical Medical Research Center of Chronic Kidney Disease, Kunming 650032, Yunnan, China., Jiang XM; Department of Nephrology & Rheumatology, Kunming Children's Hospital, Kunming 650228, Yunnan, China., Bi X; Department of Nephrology & Rheumatology, Kunming Children's Hospital, Kunming 650228, Yunnan, China., Yang MF; Department of Nephrology & Rheumatology, Kunming Children's Hospital, Kunming 650228, Yunnan, China., Zhao B; Department of Nephrology & Rheumatology, Kunming Children's Hospital, Kunming 650228, Yunnan, China. Electronic address: zbkmetyy@163.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Oct 25; Vol. 140, pp. 112755. Date of Electronic Publication: 2024 Aug 03.
DOI: 10.1016/j.intimp.2024.112755
Abstrakt: STAT3 gain-of-function syndrome, characterized by early-onset autoimmunity and primary immune regulatory disorder, remains poorly understood in terms of its immunological mechanisms. We employed whole-genome sequencing of familial trios to elucidate the pivotal role of de novo mutations in genetic diseases. We identified 37 high-risk pathogenic loci affecting 23 genes, including a novel STAT3 c.508G>A mutation. We also observed significant down-regulation of pathogenic genes in affected individuals, potentially associated with inflammatory responses regulated by PTPN14 via miR378c. These findings enhance our understanding of the pathogenesis of STAT3 gain-of-function syndrome and suggest potential therapeutic strategies. Notably, combined JAK inhibitors and IL-6R antagonists may offer promising treatment avenues for mitigating the severity of STAT3 gain-of-function syndrome.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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