Regulatory T-cells Inhibit Microglia-induced Pain Hypersensitivity in Female Mice

Overview

Journal Elife

Specialty Biology

Date 2021 Oct 15

PMID 34652270

Citations 36

Authors

Julia A Kuhn

Ilia D Vainchtein

Joao Braz

Katherine Hamel

Mollie Bernstein

Veronica Craik

Madelene W Dahlgren

Jorge Ortiz-Carpena

Ari B Molofsky

Anna V Molofsky

Allan I Basbaum

Affiliations

Soon will be listed here.

Abstract

Peripheral nerve injury-induced neuropathic pain is a chronic and debilitating condition characterized by mechanical hypersensitivity. We previously identified microglial activation via release of colony-stimulating factor 1 (CSF1) from injured sensory neurons as a mechanism contributing to nerve injury-induced pain. Here, we show that intrathecal administration of CSF1, even in the absence of injury, is sufficient to induce pain behavior, but only in male mice. Transcriptional profiling and morphologic analyses after intrathecal CSF1 showed robust immune activation in male but not female microglia. CSF1 also induced marked expansion of lymphocytes within the spinal cord meninges, with preferential expansion of regulatory T-cells (Tregs) in female mice. Consistent with the hypothesis that Tregs actively suppress microglial activation in females, Treg deficient () female mice showed increased CSF1-induced microglial activation and pain hypersensitivity equivalent to males. We conclude that sexual dimorphism in the contribution of microglia to pain results from Treg-mediated suppression of microglial activation and pain hypersensitivity in female mice.

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