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Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease

Biological aging is the strongest factor associated with the clinical phenotype of multiple sclerosis (MS). Relapsing-remitting MS typically presents in the third or fourth decade, whereas the mean age of presentation of progressive MS (PMS) is 45 years old. Here, we show that experimental autoimmun...

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Autores principales: Atkinson, Jeffrey R., Jerome, Andrew D., Sas, Andrew R., Munie, Ashley, Wang, Cankun, Ma, Anjun, Arnold, William D., Segal, Benjamin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309055/
https://www.ncbi.nlm.nih.gov/pubmed/35511417
http://dx.doi.org/10.1172/jci.insight.158153
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author Atkinson, Jeffrey R.
Jerome, Andrew D.
Sas, Andrew R.
Munie, Ashley
Wang, Cankun
Ma, Anjun
Arnold, William D.
Segal, Benjamin M.
author_facet Atkinson, Jeffrey R.
Jerome, Andrew D.
Sas, Andrew R.
Munie, Ashley
Wang, Cankun
Ma, Anjun
Arnold, William D.
Segal, Benjamin M.
author_sort Atkinson, Jeffrey R.
collection PubMed
description Biological aging is the strongest factor associated with the clinical phenotype of multiple sclerosis (MS). Relapsing-remitting MS typically presents in the third or fourth decade, whereas the mean age of presentation of progressive MS (PMS) is 45 years old. Here, we show that experimental autoimmune encephalomyelitis (EAE), induced by the adoptive transfer of encephalitogenic CD4(+) Th17 cells, was more severe, and less likely to remit, in middle-aged compared with young adult mice. Donor T cells and neutrophils were more abundant, while B cells were relatively sparse, in CNS infiltrates of the older mice. Experiments with reciprocal bone marrow chimeras demonstrated that radio-resistant, nonhematopoietic cells played a dominant role in shaping age-dependent features of the neuroinflammatory response, as well as the clinical course, during EAE. Reminiscent of PMS, EAE in middle-aged adoptive transfer recipients was characterized by widespread microglial activation. Microglia from older mice expressed a distinctive transcriptomic profile suggestive of enhanced chemokine synthesis and antigen presentation. Collectively, our findings suggest that drugs that suppress microglial activation, and acquisition or expression of aging-associated properties, may be beneficial in the treatment of progressive forms of inflammatory demyelinating disease.
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spelling pubmed-93090552022-07-27 Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease Atkinson, Jeffrey R. Jerome, Andrew D. Sas, Andrew R. Munie, Ashley Wang, Cankun Ma, Anjun Arnold, William D. Segal, Benjamin M. JCI Insight Research Article Biological aging is the strongest factor associated with the clinical phenotype of multiple sclerosis (MS). Relapsing-remitting MS typically presents in the third or fourth decade, whereas the mean age of presentation of progressive MS (PMS) is 45 years old. Here, we show that experimental autoimmune encephalomyelitis (EAE), induced by the adoptive transfer of encephalitogenic CD4(+) Th17 cells, was more severe, and less likely to remit, in middle-aged compared with young adult mice. Donor T cells and neutrophils were more abundant, while B cells were relatively sparse, in CNS infiltrates of the older mice. Experiments with reciprocal bone marrow chimeras demonstrated that radio-resistant, nonhematopoietic cells played a dominant role in shaping age-dependent features of the neuroinflammatory response, as well as the clinical course, during EAE. Reminiscent of PMS, EAE in middle-aged adoptive transfer recipients was characterized by widespread microglial activation. Microglia from older mice expressed a distinctive transcriptomic profile suggestive of enhanced chemokine synthesis and antigen presentation. Collectively, our findings suggest that drugs that suppress microglial activation, and acquisition or expression of aging-associated properties, may be beneficial in the treatment of progressive forms of inflammatory demyelinating disease. American Society for Clinical Investigation 2022-06-22 /pmc/articles/PMC9309055/ /pubmed/35511417 http://dx.doi.org/10.1172/jci.insight.158153 Text en © 2022 Atkinson et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Atkinson, Jeffrey R.
Jerome, Andrew D.
Sas, Andrew R.
Munie, Ashley
Wang, Cankun
Ma, Anjun
Arnold, William D.
Segal, Benjamin M.
Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease
title Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease
title_full Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease
title_fullStr Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease
title_full_unstemmed Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease
title_short Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease
title_sort biological aging of cns-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309055/
https://www.ncbi.nlm.nih.gov/pubmed/35511417
http://dx.doi.org/10.1172/jci.insight.158153
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