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Age-Dependent Decrease in the Induction of Regulatory T Cells Is Associated With Decreased Expression of RALDH2 in
Tomohiro Takano1, Ryutaro Kotaki1, Jihyun Park1,2
1Research Center for Food Safety, The University of Tokyo, Tokyo, Japan.
Frontiers in Immunology
|August 28, 2020
Summary
Aging impairs immune function by decreasing regulatory T cell (Treg) induction. This study reveals reduced retinoic acid (RA) production by dendritic cells (DCs) in aged mice, linked to epigenetic changes, impacting oral antigen tolerance.
Area of Science:
- Immunology
- Aging research
- Gastroenterology
Background:
- Immune function declines with age, leading to chronic inflammation and age-related diseases.
- Regulatory T cells (Tregs) are crucial for immune tolerance, and their induction decreases with age.
- Dendritic cells (DCs) in the intestine induce Tregs via retinoic acid (RA) production, catalyzed by retinaldehyde dehydrogenase 2 (RALDH2).
Purpose of the Study:
- To investigate the mechanisms underlying the age-related decline in antigen-specific Treg induction.
- To identify changes in dendritic cell subsets and RALDH2 expression in aged mice.
- To explore the role of epigenetic modifications in regulating RALDH2 expression and Treg induction.
Main Methods:
- Comparison of Treg induction in young and aged mice after oral antigen administration.
- Analysis of dendritic cell subsets (CD11b, CD103, PD-L1) in mesenteric lymph nodes (MLNs).
- Measurement of RALDH2 gene expression, RALDH enzyme activity, and DNA methylation in MLN DCs.
- Assessment of RA treatment effects on Treg induction.
Main Results:
- Antigen-specific Treg induction was significantly decreased in aged mice.
- MLN DCs from aged mice showed reduced RALDH2 gene expression and enzyme activity.
- A decrease in the CD11b-CD103+PD-L1high DC subset and increased methylation of the RALDH2 promoter were observed in aged mice.
- RA treatment showed a trend towards increased Treg induction.
Conclusions:
- The age-related decrease in Treg induction is associated with impaired RA production by MLN DCs, potentially due to epigenetic silencing of RALDH2.
- Specific DC subsets and their RA-producing capacity are diminished with age.
- Restoring RA production may be a therapeutic strategy to enhance immune tolerance in aging individuals.
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