Thymus-derived Foxp3⁺ regulatory T cells upregulate RORγt expression under inflammatory conditions

Area of Science:

• Immunology
• Cell Biology

Background:

• Foxp3+ regulatory T cells (Tregs) co-expressing RORγt are linked to gut microbiota responses.
• RORγt+ Tregs were previously thought to be solely peripherally induced (pTregs).

Purpose of the Study:

• To investigate the origin of RORγt+ Tregs.
• To determine if thymus-derived Tregs (tTregs) can express RORγt.

Main Methods:

• Utilized transgenic Foxp3∆CNS1-Cre reporter mice.
• Analyzed CNS1-independent Tregs for RORγt co-expression.
• Isolated genuine tTregs from Foxp3hCD2RAGGFP reporter mice.
• Assessed RORγt expression in vitro and in vivo under inflammatory conditions.

Main Results:

• A significant fraction of CNS1-independent Tregs, primarily tTregs, co-expressed RORγt.
• Genuine tTregs demonstrated RORγt induction in vitro and in vivo, especially during inflammation.
• RORγt is not exclusive to peripherally induced Tregs.

Conclusions:

• Thymus-derived Tregs (tTregs) can upregulate RORγt expression.
• RORγt+ Tregs represent a heterogeneous population comprising both pTregs and tTregs.
• RORγt is not a definitive marker for peripherally induced Tregs.