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).