Editors' ChoiceNeuroimmunology

A healthy dose of fear

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Science Signaling  13 Oct 2020:
Vol. 13, Issue 653, eabf1712
DOI: 10.1126/scisignal.abf1712

Secretion of IL-17a from meninges-resident T cells promotes anxiety-like behavior in mice.

Immune cells in the meninges (the lining around the brain) defend the brain from pathogenic infection. Cytokines secreted from meningeal immune cells—particularly IL-17A from γδ T cells—also affect learning and sociability in mice. Alves de Lima et al. (see also Rua and Pujol) confirmed the presence of γδ T cells in the meninges of humans and mice and characterized the postnatal meningeal origins and maintenance of these cells in mice. Unexpectedly, however, in vivo fluorescent tracking of IL-17A revealed that meningeal γδ T cells produced the cytokine even in the absence of infection. When placed into open-field and cross-maze behavior tests, mice lacking γδ T cells or glutamatergic neuron–specific IL-17A receptors exhibited less anxiety-like behavior than did wild-type mice. Similarly, injecting IL-17A–neutralizing antibodies into the cerebrospinal fluid decreased anxiety-like behavior in wild-type mice. Basal expression of IL-17A appeared to be influenced by commensal microbiota, because either broad-spectrum antibiotic treatment or the use of germ-free mice decreased Il17a transcription while not affecting meningeal γδ17 T cell numbers. In mice, as in humans, anxiety and fear-associated behavior (to an extent) has evolved as a protective, survival mechanism. Thus, these findings suggest that IL-17A production by meningeal γδ T cells may have evolved to modify fear behavior as well as the body’s immune response to infection, and that this mechanism may be influenced by host commensal microbiota.

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