Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Narasimhan, Hamsa ; Richter, Maria L. ; Shakiba, Ramin ; Papaioannou, Nikos E. ; Stehle, Christina ; Rengarajan, Kaushikk Ravi ; Ulmert, Isabel LU ; Kendirli, Arek ; de la Rosa, Clara and Kuo, Pin Yu , et al. (2025) In Proceedings of the National Academy of Sciences of the United States of America 122(9).
Abstract

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+... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AIRE, antigen presenting cells, dendritic cells, innate lymphocytes, RORγt
in
Proceedings of the National Academy of Sciences of the United States of America
volume
122
issue
9
article number
e2417308122
publisher
National Academy of Sciences
external identifiers
  • pmid:39993193
  • scopus:85219601765
ISSN
0027-8424
DOI
10.1073/pnas.2417308122
language
English
LU publication?
yes
id
6b31a785-6da6-4894-8e74-f63a01887473
date added to LUP
2025-06-23 11:13:58
date last changed
2025-07-21 12:30:13
@article{6b31a785-6da6-4894-8e74-f63a01887473,
  abstract     = {{<p>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<sup>+</sup> DCs are a conserved, functionally versatile, and transcriptionally distinct type of DCs. RORγt<sup>+</sup> DCs entail various populations described in different contexts including Janus cells/RORγt-expressing extrathymic Aire-expressing cells (eTACs), subtypes of Thetis cells, RORγt<sup>+</sup>-DC (R-DC) like cells, cDC2C and ACY3<sup>+</sup> DCs. We show that in response to inflammatory triggers, RORγt<sup>+</sup> DCs can migrate to lymph nodes and in the spleen can activate naïve CD4<sup>+</sup> T cells. These findings expand the functional repertoire of RORγt<sup>+</sup> 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<sup>+</sup> DCs with proinflammatory features accumulate in autoimmune neuroinflammation in mice and men. Thus, our work establishes RORγt<sup>+</sup> 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.</p>}},
  author       = {{Narasimhan, Hamsa and Richter, Maria L. and Shakiba, Ramin and Papaioannou, Nikos E. and Stehle, Christina and Rengarajan, Kaushikk Ravi and Ulmert, Isabel and Kendirli, Arek and de la Rosa, Clara and Kuo, Pin Yu and Altman, Abigail and Münch, Philipp and Mahboubi, Saba and Küntzel, Vanessa and Sayed, Amina and Stange, Eva Lena and Pes, Jonas and Antonova, Alina Ulezko and Pereira, Carlos Filipe and Klein, Ludger and Dudziak, Diana and Colonna, Marco and Torow, Natalia and Hornef, Mathias W. and Clausen, Björn E. and Kerschensteiner, Martin and Lahl, Katharina and Romagnani, Chiara and Colomé-Tatché, Maria and Schraml, Barbara U.}},
  issn         = {{0027-8424}},
  keywords     = {{AIRE; antigen presenting cells; dendritic cells; innate lymphocytes; RORγt}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells}},
  url          = {{http://dx.doi.org/10.1073/pnas.2417308122}},
  doi          = {{10.1073/pnas.2417308122}},
  volume       = {{122}},
  year         = {{2025}},
}