Patients informing immunobiology: How disorders of IL-21 receptor signaling unravel pathways of CD8 T-cell function

摘要

The study of monogenic diseases of the immune system can help decipher fundamental mechanisms in immunobiology by identifying new immune pathways, clarifying the role of affected molecules in known pathways, and often highlighting differences in gene function between human subjects and nonhuman models. Although extraordinarily rare, clinical entities caused by abnormal cytokine signaling are a group of such disorders that can be highly instructive in this regard. IL-21 is a cytokine responsible for pleiotropic effects on multiple cell lineages of the immune system. Signal transducer and activator of transcription (STAT) 3 and STAT1 appear to propagate IL-21 signaling through the IL-21 receptor (IL-21 R) in a variety of cell types.1 As such, study of patients with STAT1 deficiency, STAT3 deficiency and autosomal dominant hyper-IgE syndrome (AD-HIES), and the recently identified IL-21R deficiency2 all allow for the dissection of the role of this pathway in immune functions.