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A distinct human cell type expressing MHCII and RORγt with dual characteristics of dendritic cells and type 3 innate lymphoid cells.
Ulezko Antonova, Alina; Lonardi, Silvia; Monti, Matilde; Missale, Francesco; Fan, Changxu; Coates, Matthew L; Bugatti, Mattia; Jaeger, Natalia; Fernandes Rodrigues, Patrick; Brioschi, Simone; Trsan, Tihana; Fachi, José L; Nguyen, Khai M; Nunley, Ryan M; Moratto, Daniele; Zini, Stefania; Kong, Lingjia; Deguine, Jacques; Peeples, Mark E; Xavier, Ramnik J; Clatworthy, Menna R; Wang, Ting; Cella, Marina; Vermi, William; Colonna, Marco.
Afiliação
  • Ulezko Antonova A; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110.
  • Lonardi S; Department of Molecular and Translational Medicine, University of Brescia, Brescia 25125, Italy.
  • Monti M; Department of Molecular and Translational Medicine, University of Brescia, Brescia 25125, Italy.
  • Missale F; Department of Molecular and Translational Medicine, University of Brescia, Brescia 25125, Italy.
  • Fan C; Department of Head & Neck Oncology & Surgery Otorhinolaryngology, Antoni Van Leeuwenhoek Nederlands Kanker Instituut, Amsterdam 1066, The Netherlands.
  • Coates ML; Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110.
  • Bugatti M; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom.
  • Jaeger N; Cambridge University Hospitals National Health Service Foundation Trust, Cambridge CB2 0QQ, United Kingdom.
  • Fernandes Rodrigues P; Department of Molecular and Translational Medicine, University of Brescia, Brescia 25125, Italy.
  • Brioschi S; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110.
  • Trsan T; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110.
  • Fachi JL; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110.
  • Nguyen KM; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110.
  • Nunley RM; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110.
  • Moratto D; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110.
  • Zini S; Washington University Orthopedics, Barnes Jewish Hospital, Saint Louis, MO 63110.
  • Kong L; Department of Lab Diagnostics, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia, Brescia 25100, Italy.
  • Deguine J; Department of Molecular and Translational Medicine, University of Brescia, Brescia 25125, Italy.
  • Peeples ME; Immunology Program, Broad Institute of Massachussets Institute of Technology and Harvard, Cambridge, MA 02142.
  • Xavier RJ; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
  • Clatworthy MR; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114.
  • Wang T; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
  • Cella M; Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210.
  • Vermi W; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
  • Colonna M; Department of Pediatrics, The Ohio State University, Columbus, OH 43210.
Proc Natl Acad Sci U S A ; 120(52): e2318710120, 2023 Dec 26.
Article em En | MEDLINE | ID: mdl-38109523
ABSTRACT
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 the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs. While RORγt+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. Herein, we identify a rare subset of RORγt+ cells with dendritic cell (DC) features through integrated single-cell RNA sequencing and single-cell ATAC sequencing. These cells, which we term RORγt+ DC-like cells (R-DC-like), exhibit DC morphology, express the MHC class II machinery, and are distinct from all previously reported DC and ILC3 subsets, but share transcriptional and epigenetic similarities with DC2 and ILC3. We have developed procedures to isolate and expand them in vitro, enabling their functional characterization. R-DC-like cells proliferate in vitro, continue to express RORγt, and differentiate into CD1c+ DC2-like cells. They stimulate the proliferation of allogeneic T cells. The identification of human R-DC-like cells with proliferative potential and plasticity toward CD1c+ DC2-like cells will prompt further investigation into their impact on immune homeostasis, inflammation, and autoimmunity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos / Imunidade Inata Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos / Imunidade Inata Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article