Abstract
In the previous study, we found that the levels of IL-21 in nasal polyps (NPs) were significantly increased and associated with polyp size and recurrence. However, it is unclear that the cell source of IL-21 and the regulation of IL-21 in NP tissues. In the present study, we isolated the lymphocytes from NP tissues, uncinate tissues and peripheral blood of patients with NPs. The cells were analyzed for cell surface markers, cytokines and transcriptional factors by flow cytometry. The results indicated that CD4+ T cells were the major IL-21-exprssing cells in NP tissues and the majority of IL-21 producing CD4+ T cells co-expressed IFN-γ or IL-17A. IL-21+IFN-γ+CD4+ T cells in NP tissues exhibited the features of both Tfh and Th1 cells which co-expressed significantly higher amount of CXCR5, ICOS, PD-1, Bcl-6 and T-bet than did IL-21+IFN-γ−CD4+ T cells (p < 0.05). Treatment of the lymphocytes from NP tissues with IL-12 enhanced the production of IL-21 and IFN-γ, especially the frequency of IL-21+IFN−γ+CD4+ T cells (p < 0.05). The blockade of IL-12 inhibited the production of IL-21 and IFN-γ (p < 0.05). These findings indicated that IL-12 positively enhanced the generation of IL-21+IFN-γ+CD4+ T cells having the features of both Tfh and Th1 cells in NP tissues.
Highlights
Basic mechanisms that control IL-21 expression in Nasal polyps (NPs) tissues are not clear
We examined whether IL-21+IFN-γ +CD4+ T cells in NP tissues have the characteristics of T follicular helper (Tfh) cells and Th1 cells
The results indicated that IFN-γ +IL-21+ T cells expressed higher levels of CXCR5, PD-1 and ICOS compared to IFN-γ +IL-21− T cells in CD4+ T cells of NP tissues (Fig. 5)
Summary
IL-21 was produced and expressed mainly by CD4+ T cells in human NP tissues. Interleukin-21 is a cytokine that has broad effects on both innate and adaptive immune responses. FACS analysis indicated that there were higher percentages of IFN-γ - and IL-17A-producing cells in CD4+ T cells from NP tissues than uncinate tissues and the expression levels of IL-4 in CD4+ T cells were no significantly changed between two groups (Fig. 3A). The expression of CXCR5, PD-1 and ICOS on CD4+ T cells in NP tissues was significantly increased compared to PBMCs and uncinate tissues (Fig. 4A,B). The results indicated that IFN-γ +IL-21+ T cells expressed higher levels of CXCR5, PD-1 and ICOS compared to IFN-γ +IL-21− T cells in CD4+ T cells of NP tissues (Fig. 5). The further analysis of cells showed that the addition of exogenous IL-12 significantly increased the percentages of IL-21 and IFN-γ double positive CD4+ T cells (Fig. 7E,F). The generation of IL-21 and IFN-γ after blocking the effect of IL-12 with anti-IL-12Rβ 1 mAb was inhibited
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