Table 1.

Characteristic immune phenotypes of Jak deficiencies

	Tyk2 deficiency	Jak3 deficiency
Lymphocyte development and proliferation	Not affected	T cell development ↓↓ T cell proliferation ↓↓
DC differentiation	IL-12 ↓, IL-23 ↓(in response to TLR4 or TLR9 activation)	Number of CD11c+ DC ↓ IL-12 ↑, IL-10 ↑(in response to TLR4 or TLR9 activation)
Pro-inflammatory Th cell responses	IL-12 signaling ↓ IFN signaling ↓ Susceptibility to viral infections ↑	IFN-g production ↓(by epigenetic modification of the IFN-g locus)
Th2 responses	IL-4 ↑ IgE ↑	IL-4 signaling ↓
Phenotype in humans	Susceptibility to infections ↑ HIES-like disease	SCID

The only viable Jak deficiencies, Tyk2 and Jak3, show distinct immune phenotypes. Whereas in the absence of Tyk2 pro-inflammatory immune responses are impaired and Th2 responses enhanced, Jak3-deficient individuals are primarily characterized by severe immunodeficiency.