Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Biophysics and Physiology, Biologic Institutes of Sciences, Federal University of Minas Gerais, Brazil.
Brain Behav Immun. 2024 Mar;117:242-254. doi: 10.1016/j.bbi.2024.01.214. Epub 2024 Jan 26.
Intestinal γδ T cells play an important role in shaping the gut microbiota, which is critical not only for maintaining intestinal homeostasis but also for controlling brain function and behavior. Here, we found that mice deficient for γδ T cells (γδ) developed an abnormal pattern of repetitive/compulsive (R/C) behavior, which was dependent on the gut microbiota. Colonization of WT mice with γδ microbiota induced R/C behavior whereas colonization of γδ mice with WT microbiota abolished the R/C behavior. Moreover, γδ mice had elevated levels of the microbial metabolite 3-phenylpropanoic acid in their cecum, which is a precursor to hippurate (HIP), a metabolite we found to be elevated in the CSF. HIP reaches the striatum and activates dopamine type 1 (D1R)-expressing neurons, leading to R/C behavior. Altogether, these data suggest that intestinal γδ T cells shape the gut microbiota and their metabolites and prevent dysfunctions of the striatum associated with behavior modulation.
肠道 γδ T 细胞在塑造肠道微生物群方面发挥着重要作用，这不仅对于维持肠道内环境稳态至关重要，而且对于控制大脑功能和行为也至关重要。在这里，我们发现缺乏 γδ T 细胞（γδ）的小鼠表现出异常的重复/强迫（R/C）行为模式，这种行为模式依赖于肠道微生物群。用 WT 微生物群定植 γδ 缺陷型小鼠会诱导 R/C 行为，而用 WT 微生物群定植 γδ 小鼠则会消除 R/C 行为。此外，γδ 小鼠的盲肠中 3-苯丙酸的水平升高，而 3-苯丙酸是 hippurate（HIP）的前体，我们发现 HIP 在 CSF 中升高。HIP 到达纹状体并激活表达多巴胺 D1 受体（D1R）的神经元，导致 R/C 行为。总的来说，这些数据表明肠道 γδ T 细胞塑造了肠道微生物群及其代谢产物，并防止了与行为调节相关的纹状体功能障碍。
