TYK2 deficiency disturbs homeostasis of lymphocytes
Cytokines signaling plays essential roles in controlling homeostasis of immune system [18]. The impairment of various cytokines signaling in TYK2 deficient patients could lead to disruption of this balance. P1 had decreased CD4+ T cells, especially the CD4 naïve cells, while his CD4 CM (central memory) and CD4 EM (effect memory) cells were increased. Besides, total B cells of P1 was degressive with elevated naïve B cells and transitional B cells (Supplementary Table 3). In P2, except for the decline of NK cells, the subsets of T cells and B cells were normal (Supplementary Table 3). Although the subsets of T cells in P3 were normal, B cells were significantly different from those in normal subjects. The total B cells, memory B cells and plasmablasts B cells were declined but the naïve B cells and the transitional B cells were higher than normal range (Supplementary Table 3). Similar to P1, P5 had abnormal T cells, the total T cells, CD4+ T cells, CD8+ T cells were significantly decreased, B cells and NK cells were normal (Supplementary Table 3).
Further analysis of CD4+T cell subsets showed that frequencies of Th1 and Th1-like cells were increased in P1 and P2 (Fig. 5A-5F), while frequency of Th2 cells was decreased in P1, P2 and P3 compared to healthy controls (Fig. 5A-5F). Th17 cells seemed unaffected in all three patients tested. The frequencies of Tfh cells were elevated in P1 and P3, but normal in P2 (Fig. 5G). We further analyzed the Tfh subsets showing normal Tfr frequency and increased CXCR5+PD-1+ cells (Fig. 5H-5L and 5N). The proportion of Treg were comparable to that of healthy controls in P2 and P3, but increased in P3 (Fig. 5H-5L).
For B cell compartment, IgMhi B cells were both elevated in P2 and P3. MZ-like cells and Sm-B cells were normal in P2, but decreased in P3 (Fig. 5M and 5O-P).