One gene to rule them all - clinical perspectives of a potent suppressor of cytokine signaling - SOCS1

Front Immunol. 2024 Apr 22:15:1385190. doi: 10.3389/fimmu.2024.1385190. eCollection 2024.

Abstract

The discovery of Suppressor of Cytokine Signaling 1 (SOCS1) in 1997 marked a significant milestone in understanding the regulation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathways. Subsequent research deciphered its cellular functions, and recent insights into SOCS1 deficiencies in humans underscored its critical role in immune regulation. In humans, SOCS-haploinsufficiency (SOCS1-HI) presents a diverse clinical spectrum, encompassing autoimmune diseases, infection susceptibility, and cancer. Variability in disease manifestation, even within families sharing the same genetic variant, raises questions about clinical penetrance and the need for individualized treatments. Current therapeutic strategies include JAK inhibition, with promising results in controlling inflammation in SOCS1-HI patients. Hematopoietic stem cell transplantation and gene therapy emerge as promising avenues for curative treatments. The evolving landscape of SOCS1 research, emphasizes the need for a nuanced understanding of genetic variants and their functional consequences.

Keywords: JAKinhibitors; SOCS1; SOCS1-HI; SOCS1-immunity; monogenic hyperinflammation; multisystem immune dysregulation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy
  • Genetic Therapy
  • Haploinsufficiency
  • Humans
  • Janus Kinases / metabolism
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Signal Transduction*
  • Suppressor of Cytokine Signaling 1 Protein* / genetics
  • Suppressor of Cytokine Signaling 1 Protein* / metabolism

Substances

  • Suppressor of Cytokine Signaling 1 Protein
  • SOCS1 protein, human
  • Janus Kinases
  • STAT Transcription Factors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a Clinician scientist Fellowship from the Else-Kröner-Fresenius foundation and a TUDresden fellowship (MeDDrive) to JK, Rosemarie-Germscheid Stiftung to CS.