Gamma-delta T cells suppress microbial metabolites that activate striatal neurons and induce repetitive/compulsive behavior in mice

被引：3

作者：

Cox, Laura M. ^{[1
]}

Tatematsu, Bruna K. ^{[1
]}

Guo, Lydia ^{[1
]}

Leserve, Danielle S. ^{[1
]}

Mayrink, Julia ^{[1
]}

Oliveira, Marilia G. ^{[1
]}

Donnelly, Dustin ^{[1
]}

Fonseca, Roberta C. ^{[1
]}

Lemos, Luisa ^{[1
]}

Lanser, Toby B. ^{[1
]}

Rosa, Ana C. ^{[1
]}

Lopes, Juliana R. ^{[1
]}

Schwerdtfeger, Luke A. ^{[1
]}

Ribeiro, Gabriela F. C. ^{[1
]}

Lobo, Eduardo L. C. ^{[1
]}

Moreira, Thais G. ^{[1
]}

Oliveira, Andre G. ^{[1
,2
]}

Weiner, Howard L. ^{[1
]}

Rezende, Rafael M. ^{[1
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA

[2] Univ Fed Minas Gerais, Biol Sci Inst, Dept Physiol & Biophys, Belo Horizonte, Brazil

来源：

BRAIN BEHAVIOR AND IMMUNITY | 2024年 / 117卷

关键词：

gamma delta T cells; Behavior; Gut microbiota; Striatum; D1R-expressing neurons; ELEMENT-MEDIATED EXPRESSION; GUT MICROBIOTA; C-FOS; ASSOCIATION; DISORDER; NRF2;

D O I：

10.1016/j.bbi.2024.01.214

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Intestinal gamma delta 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 gamma delta T cells (gamma delta(-/-)) developed an abnormal pattern of repetitive/compulsive (R/C) behavior, which was dependent on the gut microbiota. Colonization of WT mice with gamma delta(-/-) microbiota induced R/C behavior whereas colonization of gamma delta(-/-) mice with WT microbiota abolished the R/C behavior. Moreover, gamma delta(-/-) 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 gamma delta T cells shape the gut microbiota and their metabolites and prevent dysfunctions of the striatum associated with behavior modulation.

引用

页码：242 / 254

页数：13

共 2 条

[1] Traditional Herbal Medicine-Derived Sulforaphene LFS-01 Reverses Colitis in Mice by Selectively Altering the Gut Microbiota and Promoting Intestinal Gamma-Delta T Cells
Li, Ming
Gao, Jiali
Tang, Yan
Liu, Meishuo
Wu, Sijin
Qu, Kunli
Long, Xiangyu
Li, Huajun
Liu, Min
Liu, Yinhui
Yuan, Jieli
Mao, Lei
Liu, Yu
Zheng, Xiliang
Wang, Erkang
Wang, Jin
Yang, Yongliang
FRONTIERS IN PHARMACOLOGY, 2018, 8
[2] HSP65 MESSENGER RNA+ MACROPHAGES AND GAMMA-DELTA T-CELLS IN INFLUENZA VIRUS-INFECTED MICE DEPLETED OF THE CD4+ AND CD8+ LYMPHOCYTE SUBSETS
ALLAN, W
CARDING, SR
EICHELBERGER, M
DOHERTY, PC
MICROBIAL PATHOGENESIS, 1993, 14 (01) : 75 - 84

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