Gut Microbiota Defines Functional Direction of Colonic Regulatory T Cells with Unique TCR Repertoires

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• Intestinal microbiota and commensal bacteria modulate regulatory T (Treg) cell function in the colon.
• The precise impact of microbiota on colonic Treg transcriptome and TCR specificities is not fully understood.

Purpose of the Study:

• To investigate how gut microbiota influences the transcriptome and TCR repertoire of colonic Treg cells.
• To identify specific Treg subsets modulated by microbiota and assess their functional and therapeutic implications.

Main Methods:

• Single-cell RNA sequencing was used to compare colonic Tregs from specific pathogen-free and germ-free mice.
• Analysis focused on transcriptional profiles, TCR specificities, and phenotypic subsets of Tregs.

Main Results:

• Microbiota drives colonic Tregs towards a distinct activated subset (PD-1-CXCR3+) not found in germ-free mice.
• Microbiota induces expansion of specific Treg clonotypes with shared transcriptional profiles.
• PD-1-CXCR3+ Tregs exhibit enhanced suppressive capacity, increased IL-10 production, and are key in managing experimental colitis.

Conclusions:

• Gut microbiota significantly shapes colonic Treg cell phenotype, transcriptome, and function.
• A microbiota-induced Treg subset (PD-1-CXCR3+) plays a critical role in regulating enteric inflammation.
• This microbiota-immune cell interaction presents a novel therapeutic target for intestinal inflammatory diseases.