Single cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation
Summary Non-lymphoid tissues (NLTs) harbour a pool of adaptive immune cells, the development and phenotype of which remains largely unexplored. Here, we used single-cell RNA-seq to characterise CD4+regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, the respective draining lymph nodes and spleen. From this data, we modelled a continuous lymphoid-to-NLT trajectory for Treg, and reconstructed the mechanisms of cell migration and NLT adaption. This revealed a shared transcriptional programme of NLT priming in both skin and colon-associated lymph nodes, followed by tissue-specific adaptation. Predicted migration kinetics were validated using a melanoma-induction model, emphasizing the relevance of key regulators and receptors, includingBatf, Rora, Ccr8, Samsn1. Finally, we profiled human blood and NLT Treg and Tmem cells, identifying cross-mammalian conserved tissue signatures. In summary, we have identified molecular signals mediating NLT Treg recruitment and tissue adaptation through the combined use of computational prediction andin vivovalidation..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 28. Aug. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Miragaia, Ricardo J [VerfasserIn] |
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| doi: |
10.1101/217489 |
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| PPN (Katalog-ID): |
XBI000200514 |
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| 100 | 1 | |a Miragaia, Ricardo J |e verfasserin |0 (orcid)0000-0002-7924-079X |4 aut | |
| 245 | 1 | 0 | |a Single cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation |
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| 520 | |a Summary Non-lymphoid tissues (NLTs) harbour a pool of adaptive immune cells, the development and phenotype of which remains largely unexplored. Here, we used single-cell RNA-seq to characterise CD4+regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, the respective draining lymph nodes and spleen. From this data, we modelled a continuous lymphoid-to-NLT trajectory for Treg, and reconstructed the mechanisms of cell migration and NLT adaption. This revealed a shared transcriptional programme of NLT priming in both skin and colon-associated lymph nodes, followed by tissue-specific adaptation. Predicted migration kinetics were validated using a melanoma-induction model, emphasizing the relevance of key regulators and receptors, includingBatf, Rora, Ccr8, Samsn1. Finally, we profiled human blood and NLT Treg and Tmem cells, identifying cross-mammalian conserved tissue signatures. In summary, we have identified molecular signals mediating NLT Treg recruitment and tissue adaptation through the combined use of computational prediction andin vivovalidation. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
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| 700 | 1 | |a Gomes, Tomás |0 (orcid)0000-0003-1333-0191 |4 aut | |
| 700 | 1 | |a Chomka, Agnieszka |4 aut | |
| 700 | 1 | |a Jardine, Laura |4 aut | |
| 700 | 1 | |a Riedel, Angela |4 aut | |
| 700 | 1 | |a Hegazy, Ahmed N. |4 aut | |
| 700 | 1 | |a Lindeman, Ida |4 aut | |
| 700 | 1 | |a Emerton, Guy |4 aut | |
| 700 | 1 | |a Krausgruber, Thomas |4 aut | |
| 700 | 1 | |a Shields, Jacqueline |4 aut | |
| 700 | 1 | |a Haniffa, Muzlifah |4 aut | |
| 700 | 1 | |a Powrie, Fiona |4 aut | |
| 700 | 1 | |a Teichmann, Sarah A. |0 (orcid)0000-0002-6294-6366 |4 aut | |
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