Common genetic heterogeneity of human interleukin-37 leads to functional variance.

摘要: Interleukin-37 (IL-37) is an inhibitory member of the IL-1 family cytokines. We previously found that balanced selection maintains common variations human IL37 gene. However, functional consequences this have yet to be validated. Here, using cells expressing exogenous IL-37 variants, including Ref and Var1 Var2, we three variants exhibited different immunoregulatory potencies in response immune stimulation. The protein level Var2 was significantly less than or Var1, despite comparable mRNA levels all variants. Further study showed rapidly degraded by a proteasome-dependent mechanism mediated enhanced polyubiquitination, leading transient upregulation after Finally, when ectopically expressed cells, exerted inhibition on proinflammatory cytokine production did other Conversely, purified extracellular variant proteins demonstrated abilities vitro. In conclusion, our reveals genetic lead immune-inhibitory potencies, primarily as result differences stability, suggesting possible involvement these various diseases.