SIRT1 deacetylates RORγt and enhances Th17 cell generation

Area of Science:

• Immunology
• Epigenetics
• Autoimmunity

Background:

• Immune self-tolerance relies on balancing effector and regulatory T cells.
• Dysregulation of T helper 17 (Th17) cells is linked to autoimmune diseases like multiple sclerosis.

Purpose of the Study:

• To investigate the role of Sirtuin 1 (SIRT1) in T helper 17 (Th17) cell function and autoimmunity.
• To determine if SIRT1 inhibition could be a therapeutic strategy for autoimmune diseases.

Main Methods:

• Studied SIRT1's effect on RORγt, the key transcription factor for Th17 cells.
• Utilized T cell-specific Sirt1 deletion and pharmacological SIRT1 inhibitors in mouse models.
• Analyzed infiltrating immune cells in a mouse model of multiple sclerosis.

Main Results:

• SIRT1 deacetylates RORγt, enhancing Th17 cell generation and pro-inflammatory function.
• T cell-specific Sirt1 deletion and SIRT1 inhibitors suppressed Th17 differentiation.
• SIRT1 inhibition demonstrated protective effects in a mouse model of multiple sclerosis.

Conclusions:

• SIRT1 plays a pro-inflammatory role in autoimmunity, contrary to previous anti-inflammatory reports.
• Targeting SIRT1 with inhibitors offers a potential therapeutic approach for autoimmune diseases such as multiple sclerosis.