A distinct human cell type expressing MHCII and RORγt with dual characteristics of dendritic cells and type 3 innate lymphoid cells

• DOI: 10.1073/pnas.2318710120
• Publication Date: 2023-12-18T20:19:04Z
• Authors: Alina Ulezko Anto...; Silvia Lonardi; Matilde Monti; Francesco Missale; Changxu Fan; Matthew L. Coates; Mattia Bugatti; Natalia Jaeger; Patrick Fernandes...; Simone Brioschi; Tihana Trsan; José L. Fachi; Khai M. Nguyen; Ryan M. Nunley; Daniele Moratto; Stefania Zini; Lingjia Kong; Jacques Deguine; Mark E. Peeples; Ramnik J. Xavier; Menna R. Clatworthy; Ting Wang; Marina Cella; William Vermi; Marco Colonna
• Keywords: Innate lymphoid cell

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in induction of peripheral regulatory T (Tregs) immune tolerance to microbiota self-antigens. These APCs encompass Janus Thetis cell subsets, some express AutoImmune REgulator (AIRE). + MHCII type 3 innate lymphoid (ILC3) also been instruction microbiota-specific Tregs. While actively investigated mice, identity function these subsets humans remain elusive. Herein, we identify a rare subset with dendritic (DC) through integrated single-cell RNA sequencing ATAC sequencing. cells, term DC-like (R-DC-like), DC morphology, MHC class II machinery, from all previously reported ILC3 but share transcriptional epigenetic similarities DC2 ILC3. We developed procedures isolate expand them vitro, enabling their functional characterization. R-DC-like proliferate continue RORγt, differentiate into CD1c DC2-like cells. They stimulate proliferation allogeneic The identification human proliferative potential plasticity toward will prompt further investigation impact on homeostasis, inflammation, autoimmunity.