Kun Wang, Xiaomei Cao, Lei Yang, Huizhi Zhu
Huixue Research Center, Anhui University of Chinese Medicine, Hefei 230038, China; College of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; Key Laboratory of Xin'an Medical Science, Ministry of Education, Anhui University of Chinese Medicine, Hefei 230038, China.
College of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230012, China.
Int Immunopharmacol. 2024 Mar 30;130:111713. doi: 10.1016/j.intimp.2024.111713. Epub 2024 Feb 22.
Asthma, a disease intricately linked to immune inflammation, is significantly influenced by the immune regulatory effect of bone mesenchymal stem cells (BMSCs). This study aims to investigate changes in the homing of BMSCs in bronchial asthma, focusing on the Notch homolog (Notch)1/Jagged1 signaling pathway's role in regulating T helper 1(Th1)/T helper 2(Th2) drift. Additionally, we further explore the effects and mechanisms of homologous BMSCs implantation in asthma-related immune inflammation. Following intervention with BMSCs, a significant improvement in the pathology of rats with asthma was observed. Simultaneously, a reduction in the expression of inflammatory cells and inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin(IL)-4, and IL-13 was observed in bronchoalveolar lavage fluid (BALF). Furthermore, there was an increase in the expression of Th1 cytokine Interferon-γ（IFN-γ）and the transcription factor T-box expressed in T cell (T-bet), while the expression of Th2 cytokine IL-13 and transcription factor GATA binding protein (GATA)-3 decreased in lung tissue. This indicates that the Th1/Th2 drift leans towards Th1, which a crucial in ameliorating asthma inflammation. Importantly, inhibition of the Notch1 signaling pathway led to an increased expression of the Stromal cell-derived factor-1(SDF-1)/C-X-C motif chemokine receptor (CXCR)4 chemokine axis. Consequently, the homing ability of bone marrow mesenchymal stem cells to asthma-affected lung tissue was significantly enhanced. BMSCs demonstrated heightened efficacy in regulating the cytokine/chemokine network and Th1/Th2 balance, thereby restoring a stable state during the immune response process in asthma. In conclusion, inhibiting the Notch signaling pathway enhances the expression of the SDF-1 and CXCR4 chemokine axis, facilitating the migration of allogeneic BMSCs to injured lung tissues. This, in turn, promotes immune regulation and improves the Th1/Th2 imbalance, thereby enhancing the therapeutic effect on asthmatic airway inflammation.
哮喘是一种与免疫炎症密切相关的疾病，受到骨髓间充质干细胞（BMSC）免疫调节作用的显著影响。本研究旨在探讨支气管哮喘中BMSC归巢的变化，重点关注Notch同源物（Notch）1/锯齿状蛋白1（Jagged1）信号通路在调节辅助性T细胞1（Th1）/辅助性T细胞2（Th2）偏移中的作用。此外，我们进一步探讨了同源BMSC植入对哮喘相关免疫炎症的影响及机制。用BMSC干预后，观察到哮喘大鼠的病理学有显著改善。同时，在支气管肺泡灌洗液（BALF）中观察到炎性细胞和炎性细胞因子（包括肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-4和IL-13）的表达降低。此外，肺组织中Th1细胞因子干扰素-γ（IFN-γ）和T细胞中表达的转录因子T盒（T-bet）的表达增加，而Th2细胞因子IL-13和转录因子GATA结合蛋白（GATA）-3的表达降低。这表明Th1/Th2偏移倾向于Th1，这对改善哮喘炎症至关重要。重要的是，Notch1信号通路的抑制导致基质细胞衍生因子-1（SDF-1）/C-X-C基序趋化因子受体（CXCR）4趋化因子轴的表达增加。因此，骨髓间充质干细胞对哮喘受累肺组织的归巢能力显著增强。BMSC在调节细胞因子/趋化因子网络和Th1/Th2平衡方面表现出更高的功效，从而在哮喘免疫反应过程中恢复稳定状态。总之，抑制Notch信号通路可增强SDF-1和CXCR4趋化因子轴的表达，促进同种异体BMSC向受损肺组织的迁移。这反过来又促进免疫调节并改善Th1/Th2失衡，从而增强对哮喘气道炎症的治疗效果。
