Furuzawa-Carballeda Janette, Hernández-Molina Gabriela, Lima Guadalupe, Rivera-Vicencio Yahaira, Férez-Blando Karen, Llorente Luis
Arthritis Res Ther. 2013;15(3):R68. doi: 10.1186/ar4245.
IL-10-producing B cells, Foxp3-expressing T cells (Tregs) and the IDO-expressing dendritic cells (pDC) are able to modulate inflammatory processes, to induce immunological tolerance and, in turn, to inhibit the pathogenesis of autoimmune disease. The aim of the study was to characterize and to enumerate peripheral IL-10--producing B cells, Tregs and pDCregs in primary Sjögren's Syndrome (pSS) patients in regard of their clinical and serologic activity.
Fifty pSS patients and 25 healthy individuals were included in the study. CD19⁺-expressing peripheral B lymphocytes were purified by positive selection. CD19⁺/CD24(hi)/CD38(hi)/IL-10-producing B cells, CD4⁺/CD25(hi)/Foxp3⁺ and CD8⁺/CD28⁺/Foxp3⁺ Tregs, as well as CCR6⁺/CD123⁺/IDO⁺ DCs, were quantitated by flow cytometry.
Immature/transitional circulating IgA⁺ IL-10-producing B cells had higher levels in pSS patients versus control group, whereas CD19⁺/CD38(hi)/IgG⁺/IL-10⁺ cells had lower percentage versus control. Indeed CD19⁺/CD24(hi)/CD38(hi)/CD5⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD10⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD20⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD27⁻/IL-10⁺, and CD19⁺/CD24(hi)/CD38(hi)/CXCR7⁺/IL-10⁺ cells had higher frequency in clinical inactive pSS patients when compared with control group. Remarkably, only percentages of CD19⁺/CD24(hi)/CD38(hi)/CD10⁺/IL-10⁺ and CD19⁺/CD24(hi)/CD38(hi)/CD27⁻/IL-10⁺ subsets were increased in pSS serologic inactive versus control group (P < 0.05). The percentage of IDO-expressing pDC cells was higher in pSS patients regardless of their clinical or serologic activity. There were no statistically significant differences in the percentage of CD4⁺/CD25(hi)/Foxp3⁺ Tregs between patient groups versus controls. Nonetheless, a decrease in the frequency of CD8⁺/CD28⁻/Foxp3⁺ Tregs was found in inactive pSS patients versus controls (P < 0.05).
The findings of this exploratory study show that clinical inactive pSS patients have an increased frequency of IL-10--producing B cells and IDO-expressing pDC cells.
产生白细胞介素 -10（IL -10）的B细胞、表达叉头框蛋白3（Foxp3）的T细胞（调节性T细胞，Tregs）以及表达吲哚胺2,3 -双加氧酶（IDO）的树突状细胞（浆细胞样树突状细胞，pDC）能够调节炎症过程，诱导免疫耐受，进而抑制自身免疫性疾病的发病机制。本研究旨在对原发性干燥综合征（pSS）患者外周血中产生IL -10的B细胞、Tregs和pDCregs进行特征分析和计数，并探讨其与临床及血清学活性的关系。
本研究纳入了50例pSS患者和25名健康个体。通过阳性选择法纯化表达CD19⁺的外周血B淋巴细胞。采用流式细胞术对CD19⁺/CD24(高表达)/CD38(高表达)/产生IL -10的B细胞、CD4⁺/CD25(高表达)/Foxp3⁺和CD8⁺/CD28⁺/Foxp3⁺ Tregs以及CCR6⁺/CD123⁺/IDO⁺树突状细胞进行定量分析。
与对照组相比，pSS患者中未成熟/过渡型循环产生IgA⁺ IL -10的B细胞水平较高，而CD19⁺/CD38(高表达)/IgG⁺/IL -10⁺细胞的百分比则较低。实际上，与对照组相比，临床非活动期pSS患者中CD19⁺/CD24(高表达)/CD38(高表达)/CD5⁺/IL -10⁺、CD19⁺/CD24(高表达)/CD38(高表达)/CD10⁺/IL -10⁺、CD19⁺/CD24(高表达)/CD38(高表达)/CD20⁺/IL -10⁺、CD19⁺/CD24(高表达)/CD38(高表达)/CD27⁻/IL -10⁺以及CD19⁺/CD24(高表达)/CD38(高表达)/CXCR7⁺/IL -10⁺细胞的频率更高。值得注意的是，与对照组相比，仅pSS血清学非活动期患者中CD19⁺/CD24(高表达)/CD38(高表达)/CD10⁺/IL -10⁺和CD19⁺/CD24(高表达)/CD38(高表达)/CD27⁻/IL -10⁺亚群的百分比增加（P < 0.05）。无论pSS患者的临床或血清学活性如何，表达IDO的pDC细胞百分比均较高。患者组与对照组之间CD4⁺/CD25(高表达)/Foxp3⁺ Tregs的百分比无统计学显著差异。然而，与对照组相比，非活动期pSS患者中CD8⁺/CD28⁻/Foxp3⁺ Tregs的频率降低（P < 0.05）。
这项探索性研究的结果表明，临床非活动期pSS患者中产生IL -10的B细胞和表达IDO的pDC细胞频率增加。
