A RORγt⁺ cell instructs gut microbiota-specific T_reg cell differentiation.

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• The gut microbiota and host immune system maintain a symbiotic relationship crucial for homeostasis.
• Imbalances in this relationship can lead to inflammatory conditions like Crohn's disease.
• Gut bacteria, such as Helicobacter species, influence adaptive immune responses, directing T cell differentiation.

Purpose of the Study:

• To investigate the specific cells and molecular mechanisms involved in induced regulatory T cell (iTreg) differentiation.
• To understand how gut bacteria direct T cells towards distinct functional fates.

Main Methods:

• Investigated antigen presentation pathways required for iTreg cell induction.
• Analyzed the role of RORγt-expressing cells in T cell differentiation.
• Examined the necessity of the antigen-presentation machinery, CCR7, and αv integrin for iTreg induction.

Main Results:

• Antigen presentation by RORγt+ cells (likely innate lymphoid cells) is required and sufficient for iTreg induction, not classical dendritic cells.
• RORγt+ cells require specific molecular components (antigen-presentation machinery, CCR7, αv integrin) for iTreg differentiation.
• Absence of these factors leads to the expansion of pathogenic T helper 17 (TH17) cells.

Conclusions:

• Intestinal microbes utilize distinct antigen-presenting cells with pre-programmed features to direct specific T cell differentiation.
• This targeted approach ensures appropriate immune responses, distinguishing between regulatory and inflammatory pathways.