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Immunosenescence of macrophages: reduced MHC class II gene expression
Carmen Herrero1, Carlos Sebastián, Laura Marqués
1Departament de Fisiologia (Biologia del Macrofag), Facultat de Biologia and Fundació August Pi i Sunyer, Universitat de Barcelona, Avenida Diagonal 645, E-08028 Barcelona, Spain.
Abstract:
In order to determine the effect of aging on macrophages, we produced bone marrow-derived macrophages in vitro from young and aged mice. We analyzed the effect of aging on the genomic expression of macrophages in these conditions, without the influence of other cell types that may be affected by aging. Macrophages from young and aged mice were present in similar numbers and showed an identical degree of differentiation, cell size, DNA content and cell surface markers. After incubation with interferon-gamma (IFN-gamma), the expression at the cell surface of the MHC class II gene IA complex product and the levels of intracellular IAbeta protein and mRNA were lower in aged macrophages. Moreover, the transcription of IAbeta gene was impaired in aged macrophages. The amount of transcription factors that bound to the W and X boxes, but not to the Y box of the IAbeta promoter gene were lower in aged macrophages. Similar levels of CIITA mRNA were found after IFN-gamma treatment of both young and aged macrophages. This shows that neither the initial cascade that starts after the interaction of IFN-gamma with the receptor, nor the second signals involved in the expression of CIITA, are impaired in aged macrophages. These data could explain, at least in part, the impaired immune response associated to senescence.
Insights
Aging impairs macrophage function by reducing MHC class II expression and IAbeta gene transcription, potentially explaining age-related immune decline. This study focused on genomic expression in macrophages from young and aged mice.
Area of Science:
- Immunology
- Cellular Biology
- Gerontology
Background:
- Macrophages are crucial immune cells affected by aging.
- Senescence can lead to impaired immune responses.
- Understanding age-related changes in macrophages is vital for immune health.
Purpose of the Study:
- To investigate the impact of aging on macrophage genomic expression.
- To analyze the effect of interferon-gamma (IFN-gamma) on macrophages from young and aged mice.
- To identify molecular mechanisms underlying age-related immune dysfunction in macrophages.
Main Methods:
- Bone marrow-derived macrophages were cultured in vitro from young and aged mice.
- Genomic expression, cell surface markers, and protein/mRNA levels were analyzed.
- Transcription factor binding to the IAbeta promoter was assessed.
Main Results:
- Aged macrophages exhibited lower cell surface MHC class II expression and intracellular IAbeta protein/mRNA levels after IFN-gamma stimulation.
- IAbeta gene transcription was impaired in aged macrophages.
- Reduced binding of transcription factors to specific promoter regions (W and X boxes) was observed in aged macrophages, while CIITA mRNA levels remained similar.
Conclusions:
- Aging impairs macrophage's ability to express MHC class II molecules, primarily due to reduced IAbeta gene transcription.
- The initial signaling cascade following IFN-gamma receptor interaction and CIITA expression are not impaired in aged macrophages.
- These findings offer insights into the mechanisms of age-associated immunosenescence and impaired immune responses.