| Title: |
RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells |
| Authors: |
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; Münch, Philipp; Mahboubi, Saba; Küntzel, 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, Björn E.; Kerschensteiner, Martin; Lahl, Katharina; Romagnani, Chiara; Colomé-Tatché, Maria; Schraml, Barbara U. |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America; 122(9), no e2417308122 (2025) ; ISSN: 0027-8424 |
| Publisher Information: |
National Academy of Sciences |
| Publication Year: |
2025 |
| Collection: |
Lund University Publications (LUP) |
| Subject Terms: |
Immunology in the Medical Area (including Cell and Immunotherapy); AIRE; antigen presenting cells; dendritic cells; innate lymphocytes; RORγt |
| Description: |
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 RORγt+ DCs are a conserved, functionally versatile, and transcriptionally distinct type of DCs. RORγt+ DCs entail various populations described in different contexts including Janus cells/RORγt-expressing extrathymic Aire-expressing cells (eTACs), subtypes of Thetis cells, RORγt+-DC (R-DC) like cells, cDC2C and ACY3+ DCs. We show that in response to inflammatory triggers, RORγt+ DCs can migrate to lymph nodes and in the spleen can activate naïve CD4+ T cells. These findings expand the functional repertoire of RORγt+ 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 RORγt+ DCs with proinflammatory features accumulate in autoimmune neuroinflammation in mice and men. Thus, our work establishes RORγt+ 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
http://dx.doi.org/10.1073/pnas.2417308122; pmid:39993193; scopus:85219601765 |
| DOI: |
10.1073/pnas.2417308122 |
| Availability: |
https://lup.lub.lu.se/record/6b31a785-6da6-4894-8e74-f63a01887473; https://doi.org/10.1073/pnas.2417308122 |
| Accession Number: |
edsbas.B7F02B89 |
| Database: |
BASE |