Metabotropic Glutamate Receptor-4 Modulates Adaptive Immunity and Restrains Neuroinflammation

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2010 Jul 27

PMID 20657581

Citations 69

Authors

Francesca Fallarino

Claudia Volpi

Francesco Fazio

Serena Notartomaso

Carmine Vacca

Carla Busceti

Silvio Bicciato

Giuseppe Battaglia

Valeria Bruno

Paolo Puccetti

Maria C Fioretti

Ferdinando Nicoletti

Ursula Grohmann

Roberto Di Marco

Affiliations

Soon will be listed here.

Abstract

High amounts of glutamate are found in the brains of people with multiple sclerosis, an inflammatory disease marked by progressive demyelination. Glutamate might affect neuroinflammation via effects on immune cells. Knockout mice lacking metabotropic glutamate receptor-4 (mGluR4) were markedly vulnerable to experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis) and developed responses dominated by interleukin-17-producing T helper (T(H)17) cells. In dendritic cells (DCs) from those mice, defective mGluR4 signaling-which would normally decrease intracellular cAMP formation-biased T(H) cell commitment to the T(H)17 phenotype. In wild-type mice, mGluR4 was constitutively expressed in all peripheral DCs, and this expression increased after cell activation. Treatment of wild-type mice with a selective mGluR4 enhancer increased EAE resistance via regulatory T (T(reg)) cells. The high amounts of glutamate in neuroinflammation might reflect a counterregulatory mechanism that is protective in nature and might be harnessed therapeutically for restricting immunopathology in multiple sclerosis.

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