全球耐药、耐多药、广泛耐药结核病的疫情日趋严峻。持续低效的抗结核治疗不仅没有有效控制病情，化疗药物引发的免疫抑制已引起临床和基础工作者的关注，而对其调控机制的研究几乎空白。我们前期研究发现：分化抑制因子1（ID1）在耐药结核病人外周血中显著升高，药物刺激免疫细胞显著诱导ID1产生并抑制炎症因子的表达；ID1可直接结合IKKβ，抑制其磷酸化，负调NF-κB通路的炎症信号，下调炎症因子的表达。本项目拟利用CRISPR Cas9，EMSA，免疫荧光共定位等技术，深入研究抗结核药物诱导ID1负调NF-κB信号通路，引起耐药结核病免疫抑制的分子机制。阐明持续给药后，药物抑制结核患者的主动免疫，造成耐药结核病难治易发的分子机制，为耐药结核病的防控提供新的理论和研究方向。

Global tuberculosis has declined overall, but drug-resistant tuberculosis has risen against the trend, especially multi-drug resistance (MDR) and extensive drug resistance (XDR). The mechanism of drug-resistant tuberculosis remains unclear. Our previous study found that differentiation inhibitor 1 (ID1) was significantly elevated in peripheral blood of drug-resistant tuberculosis. Drug-stimulated immune cells or mice showed significantmore ID1 production and lessinflammatory cytokines expression. Mechnismly, we found ID1 interacted withand inhibited IKKβ, negatively regulatinginflammatory cytokines expression. This project intends to use CRISPR/Cas9, EMSA, immunofluorescence co-localization and other techniques to study the molecular mechanism of anti-tuberculosis drug-induced ID1 negative regulation of NF-κB signaling pathway leading to peripheral immunosuppression of drug-resistant tuberculosis. The in-depth study of this mechanism reveals that after continuous administration, the drug itself deprives the immunization of tuberculosis patients, which makes the drug-resistant tuberculosis difficult to treat, and also proposes new theories and research directions for drug-resistant tuberculosis prevention and control.