IL-21 secreting cTfh cells were higher in MS patients
Aberrant secretion of inflammatory cytokines plays an important role in
autoimmune disease. We evaluated some signature cytokines, such as
IFN-γ, IL-4, IL-17 and IL-21. Our data indicate that the frequency of
IL-21 secreting PBMCs were significantly higher in MS patients than
those in HC (2.62±0.34% vs. 0.93±0.33%, p=0.0004) (Fig. 3a,c), whereas
no significant difference was observed in IFN-γ, IL-4 and IL-17
production between MS patients and HC (Fig. S1). The frequency of IL-21
secreting CD3+ T cells was higher in MS patients
compared to HC (1.95±0.32% vs. 0.81±0.49%, p=0.0009) (Fig. 3c),
whereas no significant differences in the frequencies of IL-21 producing
B cells and monocytes were observed between MS patients and HC (data not
shown). Comparative analysis of IL-21 secretion by
CD4+ T cells and CD8+ T cells showed
that significantly higher percentage of CD4+ T cells
secreted IL-21 in MS patients compared to HC (2.32±0.23% vs.
0.9±0.41%, p=0.002), while IL-21 producing CD8+ T
cells showed no significant difference between HC and MS patients (Fig.
3b, c).
Next, we analyzed the secretion of cytokines by cTfh cells and compared
their frequencies between MS patients and HC. The frequency of IL-21
secreting cTfh cells was remarkably higher in MS patients compared to HC
(8.83±1.29% vs. 3.53±1.25%, p=0.003) (Fig. 3d, e), whereas no
significant difference was observed in IFN-γ, IL-4 and IL-17 secreting
cTfh cells between MS patients and HC (Fig. S2). Comparative analysis of
IL-21 production by follicular vs. non-follicular Th cells revealed
that, higher percentage of cTfh cells secreted IL-21 compared to their
counterpart non-follicular Th cells in both HC (3.53±1.25% vs.
1.66±0.64%, p=0.06) and MS (8.83±1.29% vs. 1.35±0.25%,
p<0.0001). Interestingly, IL-21 secreting cTfh cells was
significantly higher in MS compared to HC (Fig. 3d,e). Collectively,
these findings suggest that cTfh cells may engage with elevated
secretion of IL-21 in MS patients over other immune cells.