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

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+ DCs. We show that in response to inflammatory triggers RORγt+ DCs can migrate to lymph nodes and in 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 pro-inflammatory 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 T cell tolerance to T cell activation depending on signals they integrate from their environment.

ORGANISM(S): Mus musculus (mouse)

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PROVIDER: S-BSST1322 | biostudies-other |

REPOSITORIES: biostudies-other

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

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