Inborn errors of IL-6 family cytokine responses

Curr Opin Immunol. 2021 Oct:72:135-145. doi: 10.1016/j.coi.2021.04.007. Epub 2021 May 24.

Abstract

The IL-6 family of cytokines mediates functions in host protective immunity, development of multiple organs, tissue regeneration and metabolism. Inborn errors in cytokines or cytokine receptor units highlight specific roles for IL-6, IL-11, LIF, OSM, and CLC signaling whereas incomplete loss-of-function variants in the common receptor chain GP130 encoded by IL6ST or the transcription factor STAT3, as well as genes that affect either GP130 glycosylation (PGM3) or STAT3 transcriptional control (ZNF341) lead to complex phenotypes including features of hyper-IgE syndrome. Gain-of-function variants in the GP130-STAT3 signaling pathway cause immune dysregulation disorders. Insights into IL-6 family cytokine signaling inform on therapeutic application in immune-mediated disorders and potential side effects such as infection susceptibility.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Biomarkers
  • Cytokine Receptor gp130 / metabolism
  • Gain of Function Mutation
  • Gene Expression Regulation
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genotype
  • Glycosylation
  • Humans
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism*
  • Multigene Family*
  • Organ Specificity
  • Phenotype
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism

Substances

  • Biomarkers
  • Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Transcription Factors
  • ZNF341 protein, human
  • Cytokine Receptor gp130