MHC class I and II expression and induction in oligodendrocytes varies with age

Abstract Oligodendroglia expressing major histocompatibility complex (MHC) molecules have become of central interest in multiple sclerosis (MS) research, but their role in aging is still being elucidated. Using MHC class I and II reporter mice, we compared oligodendroglial MHC expression in neonatal...

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Main Authors: Riley B. Catenacci, Danny Galleguillos, Adriana Rhodes, Sloan Phillips, Peter A. Calabresi
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-03089-2
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author Riley B. Catenacci
Danny Galleguillos
Adriana Rhodes
Sloan Phillips
Peter A. Calabresi
author_facet Riley B. Catenacci
Danny Galleguillos
Adriana Rhodes
Sloan Phillips
Peter A. Calabresi
author_sort Riley B. Catenacci
collection DOAJ
description Abstract Oligodendroglia expressing major histocompatibility complex (MHC) molecules have become of central interest in multiple sclerosis (MS) research, but their role in aging is still being elucidated. Using MHC class I and II reporter mice, we compared oligodendroglial MHC expression in neonatal, young adult (8–16 weeks), and aging (52 weeks) mice at baseline and after stereotactic delivery of AAV-GFAP-IFNγ. We found that MHC class I-expressing oligodendroglia were present in both the naïve brain and spinal cord, while MHC class II-expressing oligodendroglia were seen only in the spinal cord of aging mice at baseline. After AAV injection, MHC expression in oligodendroglia increased, recapitulating pathology seen in MS mouse models and in MS post-mortem tissue. After IFNγ-AAV injection, the abundance of MHC class I-expressing oligodendroglia did not vary with age, whereas MHC class II-expressing oligodendroglia were more abundant in aging mice than neonatal and young adult mice. Our results suggest that MHC class II-expressing oligodendroglia are more prevalent with aging, which may contribute to the mechanisms underlying progressive MS and other age-related neurodegenerative diseases with central nervous system inflammation.
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spelling doaj-art-6bcbe1a3156d443da7453a2cd906efe82025-08-20T02:00:08ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-03089-2MHC class I and II expression and induction in oligodendrocytes varies with ageRiley B. Catenacci0Danny Galleguillos1Adriana Rhodes2Sloan Phillips3Peter A. Calabresi4The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of MedicineDepartment of Neurology, Johns Hopkins University School of MedicineDepartment of Neurology, Johns Hopkins University School of MedicineDepartment of Neurology, Johns Hopkins University School of MedicineThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of MedicineAbstract Oligodendroglia expressing major histocompatibility complex (MHC) molecules have become of central interest in multiple sclerosis (MS) research, but their role in aging is still being elucidated. Using MHC class I and II reporter mice, we compared oligodendroglial MHC expression in neonatal, young adult (8–16 weeks), and aging (52 weeks) mice at baseline and after stereotactic delivery of AAV-GFAP-IFNγ. We found that MHC class I-expressing oligodendroglia were present in both the naïve brain and spinal cord, while MHC class II-expressing oligodendroglia were seen only in the spinal cord of aging mice at baseline. After AAV injection, MHC expression in oligodendroglia increased, recapitulating pathology seen in MS mouse models and in MS post-mortem tissue. After IFNγ-AAV injection, the abundance of MHC class I-expressing oligodendroglia did not vary with age, whereas MHC class II-expressing oligodendroglia were more abundant in aging mice than neonatal and young adult mice. Our results suggest that MHC class II-expressing oligodendroglia are more prevalent with aging, which may contribute to the mechanisms underlying progressive MS and other age-related neurodegenerative diseases with central nervous system inflammation.https://doi.org/10.1038/s41598-025-03089-2
spellingShingle Riley B. Catenacci
Danny Galleguillos
Adriana Rhodes
Sloan Phillips
Peter A. Calabresi
MHC class I and II expression and induction in oligodendrocytes varies with age
Scientific Reports
title MHC class I and II expression and induction in oligodendrocytes varies with age
title_full MHC class I and II expression and induction in oligodendrocytes varies with age
title_fullStr MHC class I and II expression and induction in oligodendrocytes varies with age
title_full_unstemmed MHC class I and II expression and induction in oligodendrocytes varies with age
title_short MHC class I and II expression and induction in oligodendrocytes varies with age
title_sort mhc class i and ii expression and induction in oligodendrocytes varies with age
url https://doi.org/10.1038/s41598-025-03089-2
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