Highlights of IMMUNOLOGY2026™ - Invited Program Recordings-The immune cellular network defined by RORyt

Video Transcription

Video Summary

Dan Lippman reviewed more than 20 years of work on RORγ and RORγT, nuclear receptors with key roles in immune development and function. He first described how RORγT controls thymocyte survival and lymphoid tissue inducer cells, explaining why knockout mice lack lymph nodes and Peyer’s patches. Using reporter mice, his lab then linked RORγT to IL-17-producing Th17 cells in the gut and to resistance in EAE, while also noting that some cells co-express IL-17 and IFN-γ, a more pathogenic Th17 state.<br /><br />He next discussed efforts to inhibit RORγT therapeutically, including digoxin derivatives that selectively block IL-17 without affecting IFN-γ, though clinical translation has been difficult. A major theme was the microbiota: segmented filamentous bacteria induce homeostatic Th17 cells, while pathogens and pathobionts can drive pathogenic Th17 or regulatory T cells. In tumor models, SFB-specific Th17 cells can convert into IFN-γ/TNF-producing cells and help anti-PD-1 therapy work, showing T cell plasticity.<br /><br />Finally, he described a newly defined RORγT-positive antigen-presenting cell population that induces peripheral Tregs and maintains tolerance to bacteria and food antigens. Loss of these cells leads to pathogenic Th17 expansion, colitis, and allergy-like inflammation. The talk ended with questions about how these cells are positioned and regulated in lymphoid tissues.

Keywords

RORγT

Th17 cells

immune regulation

microbiota

IL-17

Treg induction

nuclear receptors