Aging Reshapes γ/δ T-Cell Immunity Through a Type I Interferon-Foxo1 Axis.

Area of Science:

• Immunology
• Aging research
• T-cell biology

Background:

• Aging profoundly impacts immune cell function, but effects on peripheral gamma-delta T-cell subsets are not fully understood.
• Peripheral γ/δ T-cell compartment undergoes significant remodeling with age.

Purpose of the Study:

• To investigate the age-related changes in peripheral γ/δ T-cell subsets.
• To understand the functional and mechanistic alterations in aged γ/δ T cells.

Main Methods:

• Analysis of γ/δ T-cell populations in young and aged mice.
• Assessment of IL-17 production ex vivo and in vivo.
• Investigation of transcription factor Foxo1 expression.
• Examination of Type I interferon signaling pathways.

Main Results:

• Innate-like Ly-6C- CD44hi γ/δ T cells expand in aged mice, while adaptive-like subsets decrease.
• Aged Ly-6C- CD44hi γ/δ T cells show enhanced IL-17 production.
• Foxo1 expression is decreased in aged Ly-6C- CD44hi γ/δ T cells.
• Type I interferon signaling contributes to Foxo1 downregulation and enhanced IL-17 production.

Conclusions:

• Aging, via Type I interferon and Foxo1 modulation, promotes expansion and pro-inflammatory activity of innate-like γ/δ T cells.
• These changes may enhance immune surveillance but could also drive age-associated immune dysregulation and inflammation.