Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases
2021
Authors:
Stojić-Vukanić, ZoricaPilipović, Ivan
Arsenović-Ranin, Nevena
Dimitrijević, Mirjana
Leposavić, Gordana
Document Type:
Article (Published version)
,
© 2021 European Federation of Immunological Societies. Published by Elsevier B.V.
Metadata
Show full item recordAbstract:
The incidence of multiple sclerosis (MS) and susceptibility of animals to experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, decrease with aging. Generally, autoimmune diseases develop as the ultimate outcome of an imbalance between damaging immune responses against self and regulatory immune responses (keeping the former under control). Thus, in this review the age-related changes possibly underlying this balance were discussed. Specifically, considering the central role of T cells in MS/EAE, the impact of aging on overall functional capacity (reflecting both overall count and individual functional cell properties) of self-reactive conventional T cells (Tcons) and FoxP3+ regulatory T cells (Tregs), as the most potent immunoregulatory/suppressive cells, was analyzed, as well. The analysis encompasses three distinct compartments: thymus (the primary lymphoid organ responsible for the elimination of self-reactive T cells – negative selection and the generation of Tregs, compensating for imperfections of the negative selection), peripheral blood/lymphoid tissues (“afferent” compartment), and brain/spinal cord tissues (“target” compartment). Given that the incidence of MS and susceptibility of animals to EAE are greater in women/females than in age-matched men/males, sex as independent variable was also considered. In conclusion, with aging, sex-specific alterations in the balance of self-reactive Tcons/Tregs are likely to occur not only in the thymus/”afferent” compartment, but also in the “target” compartment, reflecting multifaceted changes in both T-cell types. Their in depth understanding is important not only for envisaging effects of aging, but also for designing interventions to slow-down aging without any adverse effect on incidence of autoimmune diseases.
Keywords:
Aging; CNS and lymphoid tissues; FoxP3+ regulatory T cells; Multiple sclerosis; Self-reactive conventional T cells; Sex differenceSource:
Immunology Letters, 2021, 239, 42-59Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200161 (University of Belgrade, Faculty of Pharmacy) (RS-MESTD-inst-2020-200161)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200177 (Immunology Research Centre 'Branislav Janković' Torlak, Belgrade) (RS-MESTD-inst-2020-200177)
DOI: 10.1016/j.imlet.2021.08.003
ISSN: 0165-2478
PubMed: 34418487
WoS: 000704168900006
Scopus: 2-s2.0-85113679734
URI
https://linkinghub.elsevier.com/retrieve/pii/S0165247821001309https://radar.ibiss.bg.ac.rs/handle/123456789/4479