Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.
Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Front Immunol. 2021 Mar 15;12:627535. doi: 10.3389/fimmu.2021.627535. eCollection 2021.
The expression of ( has been described as a predictive marker for anti-Tumor Necrosis Factor (TNF)-α monoclonal antibody (mAb) therapy responsiveness in patients with inflammatory bowel disease (IBD). Here we investigated expression of specifically in CD14+ monocytes in relation to anti-TNF response. The pretreatment expression levels of CD14+ monocytes of Crohn's disease (CD) patients were predictive of outcome to anti-TNF mAb therapy, with low expression associated with response to anti-TNF. FACSorting of CD14+ monocytes with different TREM-1 levels showed that differentiation towards regulatory CD206+ M2 type macrophages by anti-TNF was suppressed in CD14+ monocytes with high TREM-1 expression. Activity of the Fcγ-Receptor and autophagy pathway, both necessary for M2 type differentiation and the response to anti-TNF, were decreased in CD14+ monocytes with high expression of TREM-1. We confirmed that the activity of the Fcγ-Receptor pathway was decreased in the CD patients that did not respond to anti-TNF therapy and that it was negatively correlated with expression levels in the CD patient cohort. In conclusion, our results indicate that expression levels in CD14+ monocytes associate with decreased autophagy and FcγR activity resulting in decreased differentiation to M2 type regulatory macrophages upon anti-TNF mAb treatment, which may explain anti-TNF non-response in IBD patients with high expression levels of .
（的表达）被描述为炎症性肠病（IBD）患者对抗肿瘤坏死因子（TNF）-α单克隆抗体（mAb）治疗反应的预测标志物。在这里，我们研究了 在与抗 TNF 反应相关的 CD14+单核细胞中的特异性表达。克罗恩病（CD）患者 CD14+单核细胞的预处理 表达水平可预测抗 TNF mAb 治疗的结果，低 表达与抗 TNF 反应相关。具有不同 TREM-1 水平的 CD14+单核细胞的 FACSorting 显示，在高 TREM-1表达的 CD14+单核细胞中，抗 TNF 诱导向调节性 CD206+M2 型巨噬细胞分化受到抑制。Fcγ-受体和自噬途径的活性，这两者都是 M2 型分化和抗 TNF 反应所必需的，在高 TREM-1表达的 CD14+单核细胞中降低。我们证实，在对抗 TNF 治疗无反应的 CD 患者中，Fcγ-受体途径的活性降低，并且与 CD 患者队列中的 表达水平呈负相关。总之，我们的结果表明，CD14+单核细胞中的 表达水平与自噬和 FcγR 活性降低相关，导致抗 TNF mAb 治疗后向 M2 型调节性巨噬细胞分化减少，这可能解释了高表达 的 IBD 患者对抗 TNF 无反应的原因。
