Journal Article

RGS10 attenuates systemic immune dysregulation induced by chronic inflammatory stress

Staley, Hannah A., Tansey, Malú Gámez, Gomes, Beatriz Nuñes, Merchak, Andrea R., Dheeravath, Kruthika, Menees, Kelly B., Bolen, MacKenzie L., Coombes, Stephen A., Neighbarger, Noelle K., Jernigan, Janna E., Baty, Zachary, Holt, Jenny, Cole, Cassandra L.

2025

Overview

Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator of immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson’s Disease (PD). Interestingly, subjects with idiopathic PD display reduced levels of RGS10 in subsets of peripheral immune cells. Additionally, individuals with PD have been shown to have increased activated peripheral immune cells in cerebrospinal fluid (CSF) compared to age-matched healthy controls. However, it is unknown whether peripheral immune cells in the CSF of individuals with PD also exhibit decreased levels of RGS10. Utilizing the Michael J. Fox Foundation Parkinson’s Progression Markers Initiative (PPMI) study we found that RGS10 levels are decreased in the CSF of individuals with PD compared to healthy controls and prodromal individuals. As RGS10 levels are decreased in the CSF and circulating peripheral immune cells of individuals with PD, we hypothesized that RGS10 regulates peripheral immune cell responses to chronic systemic inflammation (CSI) prior to the onset of neurodegeneration. To test this, we induced CSI for 6 weeks in C57BL6/J mice and RGS10 KO mice to assess circulating and CNS-associated immune cell responses. We found that RGS10 deficiency synergizes with CSI to induce a bias for inflammatory and cytotoxic cell populations, a reduction in antigen presentation machinery in peripheral blood immune cells, as well as in and around the brain that is most notable in males. These results highlight RGS10 as an important regulator of the systemic immune response to CSI and implicate RGS10 as a potential contributor to the development of immune dysregulation in PD.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Aging / Animals / Antigen presentation / Biomedical and Life Sciences / Biomedicine / Brain research / Cerebrospinal fluid / Chronic systemic inflammation / Cytokines / Cytotoxicity / Disease / Female / Fox, Michael J / Health aspects / Humans / Immune dysregulation / Immune response / Immune system / Immunology / Inflammation / Inflammation - immunology / Inflammation - metabolism / Irritable bowel syndrome / Laboratory animals / Male / Medical research / Medicine, Experimental / Mice / Mice, Inbred C57BL / Mice, Knockout / Middle Aged / Movement disorders / Neurobiology / Neurodegeneration / Neurodegenerative diseases / Neuroinflammation / Neurology / Neurosciences / Parkinson Disease - cerebrospinal fluid / Parkinson Disease - immunology / Parkinson Disease - metabolism / Parkinson's disease / Pathophysiology / Peripheral blood / Physiological aspects / Proteins / Proteomics / Regulator of G protein signaling 10 (RGS10) / RGS Proteins - cerebrospinal fluid / RGS Proteins - genetics / RGS Proteins - metabolism