Nunberg Moran Y, Werner Lael, Kopylov Uri, Haberman Yael, Lahad Avishay, Weiss Batia, Shouval Dror S
Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital, Tel Hashomer.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv.
J Pediatr Gastroenterol Nutr. 2018 May;66(5):779-784. doi: 10.1097/MPG.0000000000001795.
Interleukin-10 (IL-10) is an immunoregulatory cytokine that has a central role in suppressing proinflammatory responses. Patients with deleterious mutations in interleukin (IL)-10 or IL-10 receptor (IL-10R) genes develop severe colitis and perianal disease in the first months of life. Whether IL-10R expression and signaling in pediatric- or adult-onset Crohn disease (CD) are altered is unknown. The objective of this study was to characterize IL-10R expression and IL-10R-mediated suppression in patients with CD.
Monocytes were sorted from peripheral blood mononuclear cells of patients with CD and control subjects. IL-10R expression was determined by flow cytometry. Monocytes were stimulated with lipopolysaccharide (LPS) for 3 hours in the presence of different concentrations of IL-10 to determine IL-10-mediated suppression of tumor necrosis factor α production. Signaling through the IL-10R was evaluated by quantifying STAT3 phosphorylation in response to IL-10 stimulation.
Forty-two subjects were enrolled in this study: 19 with CD and 23 controls. Stimulation of monocytes with LPS markedly increased IL-10R expression in both groups but to a much lower extent in patients with CD. In addition, IL-10-mediated suppression of TNFα production upon LPS stimulation and IL-10-induced STAT3 phosphorylation were attenuated in patients with CD versus controls. Finally, LPS-stimulated monocytes from patients with CD secreted significantly lower quantities of IL-10, compared with control monocytes.
IL-10R expression and signaling are decreased in monocytes from patients with CD. Additional studies are required to assess whether similar patterns occur in other innate immune cells, especially in the gut, and whether disease activity, medical therapy, and genetic factors modulate these findings.
白细胞介素-10（IL-10）是一种免疫调节细胞因子，在抑制促炎反应中起核心作用。白细胞介素（IL）-10或IL-10受体（IL-10R）基因发生有害突变的患者在生命的最初几个月会发生严重的结肠炎和肛周疾病。目前尚不清楚儿童或成人发病的克罗恩病（CD）中IL-10R的表达和信号传导是否发生改变。本研究的目的是对CD患者的IL-10R表达和IL-10R介导的抑制作用进行特征描述。
从CD患者和对照受试者的外周血单核细胞中分离单核细胞。通过流式细胞术测定IL-10R的表达。在不同浓度的IL-10存在下，用脂多糖（LPS）刺激单核细胞3小时，以确定IL-10介导的肿瘤坏死因子α产生的抑制作用。通过定量响应IL-10刺激的STAT3磷酸化来评估通过IL-10R的信号传导。
本研究共纳入42名受试者：19名CD患者和23名对照。LPS刺激单核细胞可使两组的IL-10R表达均显著增加，但CD患者的增加程度要低得多。此外，与对照相比，CD患者在LPS刺激后IL-10介导的TNFα产生抑制作用以及IL-10诱导的STAT3磷酸化均减弱。最后，与对照单核细胞相比，CD患者的LPS刺激单核细胞分泌的IL-10量显著更低。
CD患者单核细胞中的IL-10R表达和信号传导降低。需要进一步研究以评估其他固有免疫细胞，尤其是肠道中的免疫细胞是否存在类似模式，以及疾病活动、药物治疗和遗传因素是否会调节这些结果。
