RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells

• 成果类型: Article
• 署名作者: Narasimhan, Hamsa; Richter, Maria L.; Shakiba, Ramin; Papaioannou, Nikos E.; Stehle, Christina; Rengarajan, Kaushikk Ravi; Ulmert, Isabel; Kendirli, Arek; de la Rosa, Clara; Kuo, Pin-Yu; Altman, Abigail; Muench, Philipp; Mahboubi, Saba; Kuentzel, Vanessa; Sayed, Amina; Stange, Eva-Lena; Pes, Jonas; Antonova, Alina Ulezko; Pereira, Carlos-Filipe; Klein, Ludger; Dudziak, Diana; Colonna, Marco; Torow, Natalia; Hornef, Mathias W.; Clausen, Bjoern E.; Kerschensteiner, Martin; Lahl, Katharina; Romagnani, Chiara; Colome-Tatche, Maria; Schraml, Barbara U.
• 署名单位: University of Munich; University of Munich; University of Munich; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; Technical University of Denmark; University of Munich; University of Munich; University of Munich; University of Munich; Lund University; Johannes Gutenberg University of Mainz; Johannes Gutenberg University of Mainz; RWTH Aachen University; RWTH Aachen University Hospital; Washington University (WUSTL); Friedrich Schiller University of Jena; University of Calgary; University of Calgary; Academy of Athens; Helmholtz Association; Helmholtz-Center for Infection Research
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11512
• 发表日期: 2025-03-04
• 关键词: innate lymphoid-cells; experimental autoimmune encephalomyelitis; flt3 ligand; immunity; receptor; prdm16; activation; selection

摘要

Conventional dendritic cells (cDCs) are potent antigen- presenting cells (APCs) that integrate signals from their environment allowing them to direct situation- adapted immunity. Thereby they harbor great potential for being targeted in vaccination, autoimmunity, and cancer. Here, we use fate mapping, functional analyses, and comparative cross- species transcriptomics to show that ROR gamma t+DCs are a conserved, functionally versatile, and transcriptionally distinct type of DCs. ROR gamma t+ DCs entail various populations described in different contexts including Janus cells/ROR gamma t- expressing extrathymic Aire- expressing cells (eTACs), subtypes of Thetis cells, ROR gamma t+-DC (R- DC) like cells, cDC2C and ACY3+ DCs. We show that in response to inflammatory triggers, ROR gamma t+ DCs can migrate to lymph nodes and in the spleen can activate na & iuml;ve CD4+ T cells. These findings expand the functional repertoire of ROR gamma t+ DCs beyond the known role of eTACs and Thetis cells in inducing T cell tolerance to self- antigens and intestinal microbes in mice. We further show that ROR gamma t+ DCs with proinflammatory features accumulate in autoimmune neuroinflammation in mice and men. Thus, our work establishes ROR gamma t+ DCs as immune sentinel cells that exhibit a broad functional spectrum ranging from inducing peripheral T cell tolerance to T cell activation depending on signals they integrate from their environment.