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PNAS 107 (6): 2580-2585

Copyright © 2010 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / IMMUNOLOGY

Inhibitory role for GABA in autoimmune inflammation

Roopa Bhat a , 1 , Robert Axtell a , Ananya Mitra b , Melissa Miranda a , Christopher Lock a , Richard W. Tsien b , and Lawrence Steinman a

aDepartment of Neurology and Neurological Sciences and bDepartment of Molecular and Cellular Physiology, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305

Contributed by Richard W. Tsien, December 31, 2009 (sent for review November 30, 2009)

Abstract: GABA, the principal inhibitory neurotransmitter in the adult brain, has a parallel inhibitory role in the immune system. We demonstrate that immune cells synthesize GABA and have the machinery for GABA catabolism. Antigen-presenting cells (APCs) express functional GABA receptors and respond electrophysiologically to GABA. Thus, the immune system harbors all of the necessary constituents for GABA signaling, and GABA itself may function as a paracrine or autocrine factor. These observations led us to ask further whether manipulation of the GABA pathway influences an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Increasing GABAergic activity ameliorates ongoing paralysis in EAE via inhibition of inflammation. GABAergic agents act directly on APCs, decreasing MAPK signals and diminishing subsequent adaptive inflammatory responses to myelin proteins.

Key Words: experimental autoimmune encephalomyelitis • multiple sclerosis • neurotransmitter • antigen-presenting cells

Author contributions: R.B., R.A., A.M., C.L., and L.S. designed research; R.B., R.A., A.M., and M.M. performed research; R.B., R.A., A.M., and M.M. analyzed data; and R.B., R.A., A.M., C.L., R.W.T., and L.S. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0915139107/DCSupplemental.

1To whom correspondence may be addressed. E-mail: roopa.bhat{at}stanford.edu. or rwtsien{at}stanford.edu

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