Highlights of IMMUNOLOGY2026™ - Invited Program Recordings-Thetis cell regulation of intestinal tolerance

Video Transcription

Video Summary

The speaker discussed how specialized antigen-presenting cells in the gut shape T cell responses, especially tolerance to microbiota and food antigens in early life. Their lab identified a rare family of RORγt-expressing antigen-presenting cells, called theta cells (TCs), that drive peripheral regulatory T cell (Treg) development. Within this family, TC4 was shown to be the key tolerogenic subset because it expresses integrin beta 8, which activates TGF-β and promotes Treg differentiation. TC1 cells also contribute to tolerance, but air-expressing subsets were dispensable for food-specific Treg induction.<br /><br />The talk emphasized a “window of opportunity” in early life, when these cells are abundant in gut lymph nodes and help establish lasting tolerance. The speaker also showed that TC4 is enriched in gut-draining lymph nodes but largely absent from skin-draining nodes, which may help explain why food sensitization can occur through inflamed skin.<br /><br />Finally, the team traced TC development to a lymphoid-restricted progenitor distinct from classical dendritic cells, identifying fetal liver-derived precursors and key regulators such as PU.1 and RANK signaling. The overall conclusion was that distinct antigen-presenting cell lineages are developmentally programmed to support either tolerance or inflammation.

Keywords

antigen-presenting cells

gut tolerance

RORγt-expressing cells

theta cells

Treg differentiation

integrin beta 8

early-life immune development