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RORγt eTACs mediate oral tolerance and Treg induction
Im-Hong Sun1,2, Anita E Qualls2, Han S Yin2
1Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
The Journal of Experimental Medicine
|April 29, 2025
Summary
RORγt-lineage cells, specifically RORγt+ Aire-expressing cells (R-eTACs), are crucial for oral tolerance. These cells, expressing integrin β8, induce regulatory T cells to prevent unwanted immune responses to food antigens.
Area of Science:
- Immunology
- Cell Biology
- Oral Tolerance
Background:
- The immune system distinguishes pathogens from dietary antigens, but mechanisms are unclear.
- Oral tolerance prevents immune responses to food, crucial for health.
Purpose of the Study:
- Identify cellular players in oral tolerance.
- Investigate the role of RORγt-lineage antigen-presenting cells (APCs).
Main Methods:
- Lineage tracing and single-cell sequencing.
- Investigated RORγt-lineage APC populations: ILC3s, RORγt+ DCs, and RORγt+ Aire-expressing cells (R-eTACs).
- Assessed the necessity of R-eTACs, MHCII, and integrin β8 (Itgb8) for oral tolerance.
Main Results:
- R-eTACs, not ILC3s, are essential for oral tolerance induction.
- R-eTACs, likely myeloid-derived, uniquely express Itgb8.
- MHCII and Itgb8 on RORγt-lineage cells are required for inducing food-specific regulatory T cells (Tregs).
- Absence of R-eTACs or MHCII/Itgb8 deletion leads to T-follicular helper responses and increased antibodies.
Conclusions:
- R-eTACs are critical mediators of oral tolerance.
- Suggests R-eTACs, MHCII, and Itgb8 as novel targets for modulating immune tolerance.
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