Inborn errors of IL-6 family cytokine responses

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.

Automated summary

The IL-6 family of cytokines plays crucial roles in immune protection, organ development, tissue regeneration, and metabolism. Genetic errors in cytokines or cytokine receptor units can lead to complex phenotypes and impact diseases like hyper-IgE syndrome. Understanding the GP130-STAT3 signaling pathway can inform therapeutic approaches for immune-mediated disorders, but may also result in infection susceptibility.