Importance of Th22 Cell Disequilibrium in Immune Thrombocytopenic Purpura

Abstract

BACKGROUND The disequilibrium of T helper (Th) cells play an important role in the occurrence and development of immune thrombocytopenic purpura (ITP). Th22 cells, as a newly discovered subset of T lymphocytes, plays an important role in autoimmune disorders and inflammatory diseases. MATERIAL AND METHODS This study explored the role of different lymphocyte subsets in chronic ITP. To explore the value of Th22 cells in the diagnosis of ITP, the numbers of Th1, Th17, and Th22 cells were detected by a 4-color flow cytometric in 32 chronic ITP patients and 30 healthy controls. RESULTS Our data showed that, compared with healthy controls, the numbers of circulating Th1, Th17, and Th22 (p<0.05) cells increased significantly in ITP patients, and Th22 cells were correlated positively with Th1 cells (r=0.4041, p<0.01) and Th17 cells (r=0.4637, p<0.05). Moreover, a positive relationship was found between Th1/Th22 cells and Th1 cells (r=0.7696, p<0.001). CONCLUSIONS A disequilibrium expression profile of Th22 cells in peripheral blood was associated with pathogenesis of ITP, possibly through cooperatively working with Th17 and Th1, which may provide a novel approach for diagnosis of ITP.

Figure 1

Quantification of circulating CD4⁺IFN-γ⁺, CD4⁺IL-17A⁺, and IL-22⁺ cells in each group. (A–C) Representative four-color dot plot analyses of CD4⁺IFN-γ⁺, CD4⁺IL-17A⁺, and IL-22⁺ cells after stimulation with PMA and ionomycin. (D) Frequency of CD4⁺IFN-γ⁺, CD4⁺IL-17A⁺, and IL-22⁺ cells on the gated lymphocytes in the FSC/SSC plot in each group. Results are represented as the mean ±SD (** p<0.05). ANOVA followed by Tukey’s post hoc test was used to analyze statistical significance.

Figure 2

Percentages of circulating Th1 (IFN-γ⁺IL-17A⁻IL-22⁻), Th1/Th17 (IFN-γ⁺IL-17A⁺IL-22⁻), Th17 (IFN-γ⁻IL-17A⁺IL-22⁻, IFN-γ⁻IL-17A⁺IL-22⁺), and Th22 (IFN-γ⁻IL-17A⁻IL-22⁺) cells on CD4+cells of ITP and HC. (A–C) Representative four-color dot plot analyses of Th1, Th17, Th22, Th1/Th22, and Th1/Th17 cells. (D) Percentages of Th1 (IFN-γ⁺IL-17A⁻IL-22⁻), Th17 (IFN-γ⁻IL-17A⁺IL-22⁻, IFN-γ⁻IL-17A⁺IL-22⁺), and Th22 (IFN-γ⁻IL-17A⁻IL-22⁺) cells, Th1/Th22, and Th1/Th17 cells. Results are represented as the mean ±SD (** p<0.05). ANOVA followed by Tukey’s post hoc test was used to analyze statistical significance.

Figure 3

Correlations between Th22 cells Th17 cells, and Th1 cells in ITP patients. (A, B) A positive correlation was found between Th22 cells and Th1 cells (r=0.4041, p=0.0218) in the ITP patients but not in the controls. (C) A positive correlation was found between Th1/Th22and Th1 cells (r=0.7696, p=0.0002). (D, E) A positive correlation was found between the percentages of Th22 cells and the percentages of Th17 cells in the ITP patients (r=0.4637, p=0.0075) but not in the controls. (F) Th1/Th17 percentage was positively correlated with Th1 percentage (r=0.6652, p<0.0001). The q test was applied to determine the difference between 2 groups. If the data were abnormally distributed, H test and Nemenyi test were used. Correlation analysis depending on data distribution was analyzed by Pearson or Spearman correlation test.