肠道炎症促进微生物特异性CD4 T细胞介导的神经炎症，这一成果由伊利诺伊大学芝加哥医学院Teruyuki Sano团队经过不懈努力而取得。2025年6月18日出版的《自然》杂志发表了这一最新研究成果。

在这里，小组报道了识别肠道定植的节段丝状细菌的T细胞可以在缺乏功能性调节性T细胞的情况下诱导无主题肠和中枢神经系统的炎症。在炎症肠道中失调的肠道共生特异性CD4 T细胞（T_comm细胞）可以被允许浸润到中枢神经系统，而不管它们的抗原特异性如何，并且有可能通过分子模拟被宿主蛋白来源的中枢神经系统抗原重新刺激，从而产生高水平的GM-CSF、IFNγ和IL-17A，引发神经损伤。这些浸润的T_comm细胞通过其依赖IL-23R的脑生成程序和不依赖IL-23R的GM-CSF的产生激活小胶质细胞，从而引发中枢神经系统炎症。总之，他们的发现揭示了T_comm细胞扰动可能导致肠外炎症的潜在机制。

据介绍，微生物群已被认为是多种肠道疾病的关键因素，在炎症性肠病和神经退行性疾病等情况下，有多篇关于肠道微生物群组成变化的报道。这些微生物变化可以通过改变特定代谢物进入血液的释放来发挥全身作用，胃肠道微生物群也被报道通过激活先天和适应性免疫表现出免疫调节活性。然而，目前尚不清楚微生物群如何导致中枢神经系统（CNS）的炎症，这些微生物通常不存在。

附：英文原文

Title: Gut inflammation promotes microbiota-specific CD4 T cell-mediated neuroinflammation

Author: White, Zachary, Cabrera, Ivan, Mei, Linghan, Clevenger, Margarette, Ochoa-Raya, Andrea, Kapustka, Isabel, Dominguez, Joseph R., Zhou, Jinyan, Koster, Kevin P., Anwar, Shehata, Wang, Qianxun, Ng, Charles, Sagoshi, Shoko, Matsuo, Takashi, Jayawardena, Dulari, Kim, Seung Hyeon, Kageyama, Takahiro, Mitchell, Benjamin J., Rivera, Dante, Dudeja, Pradeep K., Lutz, Sarah E., Kim, Ki-Wook, Yoshii, Akira, Chevrier, Nicolas, Inoue, Makoto, Sano, Teruyuki

Issue&Volume: 2025-06-18

Abstract: The microbiota has been recognized as a critical contributor to various diseases1, with multiple reports of changes in the composition of the gut microbiome in contexts such as inflammatory bowel disease2,3 and neurodegenerative diseases4. These microbial shifts can exert systemic effects by altering the release of specific metabolites into the bloodstream5,6, and the gastrointestinal microbiota has also been reported to exhibit immunomodulatory activity through the activation of innate and adaptive immunity7,8. However, it remains unclear how the microbiota contributes to inflammation in the central nervous system (CNS), where these microorganisms are typically absent. Here we report that T cells that recognize gut-colonizing segmented filamentous bacteria can induce inflammation in the mouse intestine and CNS in the absence of functional regulatory T cells. Gut commensal-specific CD4 T cells (Tcomm cells) that are dysregulated in the inflamed gut can become licensed to infiltrate into the CNS regardless of their antigen specificity and have the potential to be re-stimulated by host protein-derived antigens in the CNS via molecular mimicry, whereupon they produce high levels of GM-CSF, IFNγ and IL-17A, triggering neurological damage. These infiltrated Tcomm cells initiate CNS inflammation by activating microglia through their IL-23R-dependent encephalitogenic programme and their IL-23R-independent GM-CSF production. Together, our findings reveal potential mechanisms whereby perturbation of Tcomm cells can contribute to extraintestinal inflammation.

DOI: 10.1038/s41586-025-09120-w

Source: https://www.nature.com/articles/s41586-025-09120-w