TYK2-deficient PBMC showed similar responses to IL-12 and IL-23
TYK2 associates with IL-12Rβ1, a receptor chain that is shared by IL-12
and IL-23. The second receptor chain for both cytokines (IL-12Rβ2 and
IL-23R, respectively) associates with JAK2. Biological responses are
mainly mediated by STAT4 in response to IL-12 and STAT3 in response to
IL-23 [17]. We then assessed the responses of PBMC
from TYK2-deficient patients to IL-12 and IL-23. In contrast to the
responses to IL-6 and IL-10, PBMC from P2 and P3 showed similar
impairment in response to IL-12 and IL-23 treatment (Fig. 4A-4D).
Consistently, IFN-γ production by T cells from P3 was also less compared
to healthy control when treated with BCG alone or BCG plus IL-12 (Fig.
4E). Collectively, these data shown so far indicate TYK2 deficiency can
lead to divergent clinical phenotypes possibly due to divergent
signaling defects.