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.