Human germline gain-of-function in STAT6: from severe allergic disease to lymphoma and beyond

Sharma M., Suratannon N., Leung D., BARIŞ S., Takeuchi I., Samra S., ...Daha Fazla

Trends in Immunology, cilt.45, sa.2, ss.138-153, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 45 Sayı: 2
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.it.2023.12.003
  • Dergi Adı: Trends in Immunology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, MEDLINE, Veterinary Science Database, DIALNET
  • Sayfa Sayıları: ss.138-153
  • Anahtar Kelimeler: allergic inflammation, atopic dermatitis, inborn error of immunity, precision therapeutics, primary atopic disorder, STAT6 gain-of-function
  • Marmara Üniversitesi Adresli: Evet

Özet

Signal transducer and activator of transcription (STAT)-6 is a transcription factor central to pro-allergic immune responses, although the function of human STAT6 at the whole-organism level has long remained unknown. Germline heterozygous gain-of-function (GOF) rare variants in STAT6 have been recently recognized to cause a broad and severe clinical phenotype of early-onset, multi-system allergic disease. Here, we provide an overview of the clinical presentation of STAT6-GOF disease, discussing how dysregulation of the STAT6 pathway causes severe allergic disease, and identifying possible targeted treatment approaches. Finally, we explore the mechanistic overlap between STAT6-GOF disease and other monogenic atopic disorders, and how this group of inborn errors of immunity (IEIs) powerfully inform our fundamental understanding of common human allergic disease.