Tolerance at the Interface: RORγt⁺ Dendritic Cells Shape Mucosal Immunity

Host

Carlos Minutti, PhD, Immunoregulation Lab

Venue

Seminar Room

Abstract

Intestinal tolerance to dietary and microbial antigens depends on specialized antigen-presenting cells whose identity has been unclear. Recent studies define RORγt⁺ dendritic cells as a distinct, lymphoid-derived lineage that shares progenitors with ILC3s and is specified by a dedicated enhancer and transcriptional network. In mice, these cells are essential for inducing peripheral regulatory T cells (pTregs) in response to oral antigens; their loss results in impaired tolerance and skewing toward type 2 immunity. In humans, a rare population of RORγt⁺ MHCII⁺ dendritic-like cells with hybrid DC–ILC features has been identified in mucosal tissues, capable of activating T cells and differentiating toward conventional DC states. Together, these findings establish RORγt⁺ DCs as conserved regulators of intestinal immune homeostasis and provide a unifying framework for tolerance mechanisms in health and disease.

Bio

Marco Colonna, M.D., Professor of Pathology and Immunology at Washington University School of Medicine in St. Louis. An internationally recognized immunologist, Colonna has made fundamental contributions to our understanding of innate immunity, particularly the receptors and cellular pathways that regulate immune responses in infection, inflammation, and neurodegenerative disease. 

Trained as a physician-scientist, he has a postdoctoral training at Harvard Medical School and the Dana-Farber Cancer Institute before becoming a scientific member of the Basel Institute for Immunology in Switzerland. In 2001, he joined the faculty of Washington University School of Medicine, where he has since led a highly influential research program focused on innate immune recognition and signaling. 

Colonna’s laboratory has pioneered the discovery and characterization of several major families of immunoreceptors that regulate immune cell function. In addition to receptor biology, Colonna has made seminal contributions to the identification and functional characterization of specialized immune cell populations. More recently, Colonna’s work has expanded into neuroimmunology, where his group uncovered a critical role for the innate immune receptor TREM2 in microglial responses and susceptibility to Alzheimer's disease. His work continues to shape multiple fields, from innate immunity and mucosal immunology to neurodegeneration and tumor immunology. 

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Champalimaud Research (CR) Colloquia Series is a seminar programme organised by the Champalimaud Centre for the Unknown to promote the discussion about the most interesting and significant questions in neuroscience and physiology & cancer with appointed speakers by the CR Community.