Centro de Histocompatibilidade do Centro, Edifício São Jerónimo, 4º Piso, Praceta Mota Pinto, 3001-301 Coimbra, Portugal.
Rheumatol Int. 2012 Apr;32(4):863-9. doi: 10.1007/s00296-010-1709-6. Epub 2011 Jan 8.
With the purpose of contributing to a better knowledge of the APCs functional activity in SLE, we evaluated the distribution and functional ability to produce pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12) of peripheral blood (PB) monocytes and DC (tDC), particularly myeloid (mDC) and CD14(-/low)CD16(+) DC subpopulations comparing them with those obtained from healthy individuals. The study was performed in 34 SLE patients with diverse disease activity scores (SLEDAI) and 13 healthy age- and sex-matched controls (NC). Our results show an overall decrease in absolute number and relative frequency of tDC in SLE patients with active disease when compared to those with inactive disease and NC, although this decrease did not seem to have an effect on the distribution of PB DC subsets. The monocytes number in SLE patients was similar to those found in NC, whereas a higher frequency of monocytes producing cytokines as well as the amount of each cytokine per cell found without stimulation was particularly observed in those patients with active disease. After stimulation, we observed a higher frequency of IL-12-producing monocytes in active SLE patients. On the other hand, we found among DCs higher frequencies of cytokine-producing CD14(-/low)CD16(+) DCs and a higher amount of cytokines produced per cell, particularly in active disease. These findings support an increased production of inflammatory cytokines by APCs in active SLE, mostly associated with alterations in CD14(-/low)CD16(+) DC subset homeostasis that might contribute to explain the dynamic role of these cells in disease pathogenesis.
为了更好地了解 APC 在 SLE 中的功能活性,我们评估了外周血 (PB) 单核细胞和 DC(tDC),尤其是髓样 (mDC) 和 CD14(-/low)CD16(+) DC 亚群产生促炎细胞因子 (TNF-α、IL-1β、IL-6 和 IL-12) 的分布和功能能力,并将其与健康个体进行了比较。该研究共纳入 34 例 SLE 患者(SLEDAI 评分不同)和 13 例健康对照者(NC)。我们的结果显示,与无活动疾病和 NC 相比,活动期 SLE 患者的 tDC 绝对数量和相对频率总体下降,但这种下降似乎对 PB DC 亚群的分布没有影响。SLE 患者的单核细胞数量与 NC 相似,而活动期患者产生细胞因子的单核细胞频率更高,以及未刺激时每个细胞产生的细胞因子量也更高。刺激后,我们观察到活动期 SLE 患者产生 IL-12 的单核细胞频率更高。另一方面,我们发现 DC 中产生细胞因子的 CD14(-/low)CD16(+) DC 频率更高,每个细胞产生的细胞因子量也更高,尤其是在活动期。这些发现支持在活动期 SLE 中 APC 产生炎症细胞因子增加,这主要与 CD14(-/low)CD16(+) DC 亚群稳态的改变有关,这可能有助于解释这些细胞在疾病发病机制中的动态作用。