Logo image
Back
Macrophage Derived Small Extracellular Vesicles As Immunomodulators Of Inflammatory Pain
Abstract   Open access   Peer reviewed

Macrophage Derived Small Extracellular Vesicles As Immunomodulators Of Inflammatory Pain

Richa Pande, Renee Jean-Toussaint, Roshell Muir, Elias El Haddad and Seena Ajit
The journal of pain, v 24(4), pp 7-7
Apr 2023
DOI: https://doi.org/10.1016/j.jpain.2023.02.047
url
https://doi.org/10.1016/j.jpain.2023.02.047View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Aberrant neuroimmune signaling underlie the development of chronic pain. Small extracellular vesicles (sEVs) including exosomes are 30-150nm particles with a key role in modulating immune responses by transferring biomolecular cargo between cells. We observed that sEVs from RAW 264.7 macrophage cells show therapeutic efficacy in a complete Freud adjuvant (CFA) mouse model of inflammatory pain in both male and female mice. sEVs from antigen presenting cells (APCs) such as macrophages express major histocompatibility (MHC) and costimulatory molecules such as CD80/86 and thereby activate T cells. We hypothesize that macrophage-derived sEVs attenuate pain hypersensitivity by either directly potentiating T cell activation, or via uptake by APCs, which then display allogeneic MHC antigens, a phenomenon termed MHC cross-dressing. To test the hypothesis that sEVs can be recaptured by APCs, we investigated the effect of sEVs on activation of dendritic cells, macrophages, and T cells in splenocytes. sEV treatment upregulated MHC and CD80/86 expression on APCs and induced T cell activation in vitro. Intrathecal administration of sEV in mouse model of inflammatory pain showed a decrease in frequency of pro-inflammatory T helper 1 population and an increase in regulatory T cells. sEV treatment enhanced the release of TGF-β, and studies are ongoing to determine if miR-21 inhibition of Smad7 contribute to increase in TGF-β. Studies are also ongoing to determine if T cells are sufficient for sEV mediated inflammatory pain resolution using Rag2-/- knockout mice following adoptive transfer of these mice with CD3+ T cells along with sEVs. NIH NINDS R01 NS102836.

Metrics

31 Record Views

Details

Logo image