Impact Statement
TYK2 deficiency is a rare primary immunodeficiency disease caused by
loss of function mutations of TYK2 gene. Due to rarely reported
cases, the nature of TYK2 deficiency and the function of TYK2 in human
immune system are poorly understood. This study describes five TYK2
deficient cases presenting with or without hyper IgE levels, atopy and
distinct pathogen infection profiles, which are caused by novel TYK2
mutations. Peripheral blood mononulear cells (PBMCs) from these patients
showed heterogenous responses to various cytokines treatment, including
IFN-α/β/γ, IL-6, IL-10, IL12 and IL-23. The homeostasis of lymphocytes
is also disrupted. Based on our findings, we propose that TYK2 works as
a multi-tasker in orchestrating various cytokines signaling pathways,
differentially combined defects of which account for the expressed
clinical manifestations.