期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 12, 页码 6708-6716出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1911097117
关键词
autoimmune encephalitis; blood-brain barrier; Th17 lymphocyte; postinfectious basal ganglia encephalitis; olfactory circuitry
资金
- NIH/National Institute of Mental Health (NIMH) [R01 MH112849, R56 MH109987]
- NIH/National Institute of Neurological Disorders and Stroke [R01 NS107344]
- Leducq Foundation [15CDV02]
- NIH/NIMH [R01 MH112849]
- NIH/National Institute on Deafness and Other Communication Disorders [DC015525, R01 DC016782]
- Newport Equities LLC
Antibodies against neuronal receptors and synaptic proteins are associated with a group of ill-defined central nervous system (CNS) autoimmune diseases termed autoimmune encephalitides (AE), which are characterized by abrupt onset of seizures and/or movement and psychiatric symptoms. Basal ganglia encephalitis (BGE), representing a subset of AE syndromes, is triggered in children by repeated group A Streptococcus (GAS) infections that lead to neuropsychiatric symptoms. We have previously shown that multiple GAS infections of mice induce migration of Th17 lymphocytes from the nose into the brain, causing blood-brain barrier (BBB) breakdown, extravasation of autoantibodies into the CNS, and loss of excitatory synapses within the olfactory bulb (OB). Whether these pathologies induce functional olfactory deficits, and the mechanistic role of Th17 lymphocytes, is unknown. Here, we demonstrate that, whereas loss of excitatory synapses in the OB is transient after multiple GAS infections, functional deficits in odor processing persist. Moreover, mice lacking Th17 lymphocytes have reduced BBB leakage, microglial activation, and antibody infiltration into the CNS, and have their olfactory function partially restored. Th17 lymphocytes are therefore critical for selective CNS entry of autoantibodies, microglial activation, and neural circuit impairment during postinfectious BGE.
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