近日，美国斯坦福大学Tony Wyss-Coray、西北大学David Gate等研究人员合作发现，CD4⁺ T细胞有助于路易体痴呆症的神经变性。2021年10月14日，国际知名学术期刊《科学》在线发表了这一成果。

研究人员在路易体痴呆症（LBD）患者死后的大脑中观察到邻近路易体和多巴胺能神经元的T细胞。脑脊液（CSF）的单细胞RNA测序发现LBD中CD4⁺ T细胞的CXCR4（C-X-C Motif Chemokine Receptor 4）表达上调。CSF中CXCR4配体、CXCL12（C-X-C Motif Chemokine Ligand 12）的蛋白水平与LBD的神经轴损伤有关。此外，研究人员观察到磷酸化α-突触蛋白表位刺激的CD4⁺ T细胞的克隆扩展和白细胞介素17A的表达上调。因此，CXCR4-CXCL12信号传导可能是抑制LBD中病理性白细胞介素-17产生型T细胞运输的机制靶标。

据悉，最近的研究表明，适应性免疫系统在LBD中起作用。然而，在LBD中调节T细胞脑归巢的机制尚不清楚。

附：英文原文

Title: CD4+ T cells contribute to neurodegeneration in Lewy body dementia

Author: David Gate, Emma Tapp, Olivia Leventhal, Marian Shahid, Tim J. Nonninger, Andrew C. Yang, Katharina Strempfl, Michael S. Unger, Tobias Fehlmann, Hamilton Oh, Divya Channappa, Victor W. Henderson, Andreas Keller, Ludwig Aigner, Douglas R. Galasko, Mark M. Davis, Kathleen L. Poston, Tony Wyss-Coray

Issue&Volume: 2021-10-14

Abstract: Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in post-mortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified up-regulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C Motif Chemokine Ligand 12 (CXCL12) were associated with neuroaxonal damage in LBD. Furthermore, we observed clonal expansion and up-regulated Interleukin 17A expression by CD4+ T cells stimulated with a phosphorylated α-synuclein epitope. Thus, CXCR4-CXCL12 signaling may represent a mechanistic target for inhibiting pathological interleukin-17-producing T cell trafficking in LBD.

DOI: abf7266

Source: https://www.science.org/doi/10.1126/science.abf7266