Poster Presentation 18th International Symposium on Dendritic Cells 2026

A critical role for RORgt+ DCs in viral-mediated loss of oral tolerance (#213)

Edith E Campana 1 , Luzmariel Medina-Sanchez 1 , Ariadna Soto 1 , Halah Winner 1 , Surya Pandey 1 , Marlies Meisel 1 , Terrence Dermody 2 , Reinhard Hinterleitner 1
  1. Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
  2. Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

Celiac disease (CeD) is an autoimmune disorder characterized by loss of oral tolerance (LOT) to gluten, with maintenance of a gluten-free diet as the only treatment option. Oral tolerance is mediated by regulatory T cells (Tregs) primed by tolerogenic dendritic cells (DCs). In CeD, there is a breakdown in oral tolerance marked by insufficient gluten-specific Treg responses and expansion of gluten-specific T helper 1 (Th1) cells instead. Environmental triggers such as Type 1 Lang (T1L) reovirus have been found to trigger LOT through pro-inflammatory modulation of CD103+ CD11b- CD8a+ dendritic cells (cDC1s). Our lab has identified that colonization with Tritrichomonas arnold (T.arnold), a novel commensal gut protist, confers protection against T1L-LOT by restraining pro-inflammatory cDC1s. However, the cellular mechanisms driving T.arnold-dependent protection against viral-induced LOT is poorly understood. Recent literature has identified retinoid orphan receptor gamma t (RORgt+) DCs as critical for oral tolerance. These cells are distinct from other DCs for their expression of Prdm16, a transcription factor, and their enrichment in early life. Here, we investigated the role of the RORgt+ DCs in T1L-LOT. Our preliminary data demonstrates that T1L infection induces CD86 expression, a DC activation marker, in vivo. Moreover, T1L infection induces LOT in young mice, despite reported enrichment of RORgt+ DCs. Future studies are underway to determine whether RORgt+ DCs are required for T.arnold-mediated protection. Altogether, our findings highlight RORgt+ DCs as key regulators in T1L-LOT providing insights on the cellular mechanisms maintaining oral tolerance.