Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy.
Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy.
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DOI：
10.1038/s12276-023-01075-0
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发表时间：
2023-09
影响因子：
12.8
通讯作者：
Sharpe, Arlene H.
中科院分区：
文献类型：
--
作者：
Park, Joon Seok;Gazzaniga, Francesca S.;Kasper, Dennis L.;Sharpe, Arlene H.
我们的身体里居住着数万亿的微生物。宿主免疫系统不断与屏障器官（包括肠道）中的微生物群相互作用。几十年来，许多研究表明，我们的粘膜免疫系统是由各种微生物群来源的信号动态塑造的。阐明这些相互作用的介质是理解微生物群如何与粘膜免疫稳态和肠道相关疾病联系在一起的重要一步。有趣的是，操纵共刺激和共抑制途径的癌症免疫疗法的功效与肠道微生物群相关。此外，这些疗法在肠道中的不良反应与肠道免疫系统的失调有关。这些发现表明，免疫系统中的共刺激途径可能是宿主免疫系统和肠道微生物群之间的桥梁。在这里，我们回顾了肠道微生物的信号免疫细胞及其潜在的影响共刺激的机制。我们强调如何共刺激途径调节粘膜免疫系统，不仅通过经典的抗原呈递细胞，但也先天淋巴细胞，这是高度富集的屏障器官。最后，我们讨论了免疫检查点抑制剂在肠道中的不良影响以及与肠道微生物群的可能关系。“通过先天免疫传感器和免疫治疗的影响，共刺激和共抑制途径的微生物群依赖性调节”强调了肠道微生物在免疫细胞调节中的作用。研究人员已经证明，某些人类细菌及其产物可以影响结肠，小肠和其他器官中免疫细胞的丰度和分化。宿主免疫系统可以通过进化上保守的蛋白质来感知某些肠道微生物的存在，这些蛋白质可以与特定的细菌分子结合。宿主-微生物群相互作用导致共刺激和共抑制分子表达的变化，从而在各种情况下形成免疫。肠道微生物群通过共刺激和共抑制途径与癌症免疫疗法的反应及其不良反应有关。了解这些免疫调节机制可能会导致开发用于多种疾病的疗法。
Our bodies are inhabited by trillions of microorganisms. The host immune system constantly interacts with the microbiota in barrier organs, including the intestines. Over decades, numerous studies have shown that our mucosal immune system is dynamically shaped by a variety of microbiota-derived signals. Elucidating the mediators of these interactions is an important step for understanding how the microbiota is linked to mucosal immune homeostasis and gut-associated diseases. Interestingly, the efficacy of cancer immunotherapies that manipulate costimulatory and coinhibitory pathways has been correlated with the gut microbiota. Moreover, adverse effects of these therapies in the gut are linked to dysregulation of the intestinal immune system. These findings suggest that costimulatory pathways in the immune system might serve as a bridge between the host immune system and the gut microbiota. Here, we review mechanisms by which commensal microorganisms signal immune cells and their potential impact on costimulation. We highlight how costimulatory pathways modulate the mucosal immune system through not only classical antigen-presenting cells but also innate lymphocytes, which are highly enriched in barrier organs. Finally, we discuss the adverse effects of immune checkpoint inhibitors in the gut and the possible relationship with the gut microbiota. "Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy," highlights the role of commensal microbes in immune cell regulation. Researchers have demonstrated that certain human bacteria and their products can influence abundance and differentiation of immune cells in the colon, small intestine, and other organs. The host immune system can sense the presence of certain gut microbes through evolutionarily conserved proteins, which can bind to specific bacterial molecules. The host-microbiota interaction leads to changes in expression of costimulatory and coinhibitory molecules, shaping immunity in various contexts. The gut microbiota is linked to responses to cancer immunotherapy and its adverse effects via costimulatory and coinhibitory pathways. Understanding these immunomodulatory mechanisms could lead to the development of therapies for a wide range of diseases.
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DOI：
10.1038/nri3405
发表时间：
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期刊：
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影响因子：
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