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

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(9)

Published: Feb. 24, 2025

Conventional dendritic cells (cDCs) are potent antigen-presenting (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, comparative cross-species transcriptomics show RORγt + DCs a conserved, functionally versatile, transcriptionally distinct type of DCs. entail various populations described different contexts including Janus cells/RORγt-expressing extrathymic Aire-expressing (eTACs), subtypes Thetis cells, -DC (R-DC) like cDC2C ACY3 We response inflammatory triggers, can migrate lymph nodes the spleen activate naïve CD4 T cells. These findings expand repertoire beyond known role eTACs inducing cell tolerance self-antigens intestinal microbes mice. further with proinflammatory features accumulate autoimmune neuroinflammation mice men. Thus, our work establishes as immune sentinel exhibit broad spectrum ranging peripheral activation depending on environment.

Language: Английский

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Identification of antigen-presenting cell–T cell interactions driving immune responses to food

Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

The intestinal immune system must concomitantly tolerate food and commensals protect against pathogens. Antigen-presenting cells (APCs) orchestrate these responses by presenting luminal antigens to CD4 + T inducing their differentiation into regulatory (pTreg) or inflammatory (Th) subsets. We used a proximity labeling method (LIPSTIC) identify APCs that presented dietary under tolerizing conditions understand cellular mechanisms which tolerance is induced can be disrupted infection. Helminth infections induction proportionally the reduction in ratio between tolerogenic APCs, including migratory dendritic (cDC1s) Rorγt were primarily cDC2s. These cDC2s expanded helminth infection did not present antigens, thus avoiding diet-specific Th2 responses.

Language: Английский

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Loss of tolerance to dietary proteins: From mouse models to human model diseases

Immunological Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

The critical importance of the immunoregulatory mechanisms, which prevent adverse responses to dietary proteins is demonstrated by consequences their failure in two common but distinct human pathological conditions, food allergy and celiac disease. mechanisms tolerance have been extensively studied mouse models extent results mice can be extrapolated humans remains unclear. Here, after summarizing known control oral models, we discuss how monogenic immune disorders associated with on one hand, disease, other represent model diseases gain insight into key pathways that antigens humans. spectrum disorders, dysfunction a single gene, strongly TH2-mediated suggests an important overlap between regulate TH2 IgE mice. In contrast, disease provides unique example link autoimmunity loss antigen.

Language: Английский

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Development of Regulatory T Cells in the Thymus and Periphery

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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