| Autor: |
James Davies, Sofia Sirvent, Andres F. Vallejo, Kalum Clayton, Gemma Douilhet, Patrick S. Keeler, Jonathan West, Michael Ardern-Jones, Ben D. MacArthur, Harinder Singh, Marta E. Polak |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology. 13 |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2022.892254 |
| Popis: |
Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis revealed that steady-state LCs exist in a continuum of maturation states and upregulate antigen presentation genes along with an immunoregulatory module including the genes IDO1, LGALS1, LAMTOR1, IL4I, upon their migration. The migration-induced transition in genomic state is accompanied by the ability of LCs to more efficiently prime regulatory T cell responses in co-culture assays. Computational analyses of the scRNAseq datasets using SCENIC and Partial Information Decomposition in Context identified a set of migration-induced transcription factors including IRF4, KLF6 and RelB as key nodes within a immunoregulatory gene regulatory network. These findings support a model in which efficient priming of immunoregulatory responses by LCs is dependent on coordinated upregulation of a migration-coupled maturation program with a immunoregulation-promoting genomic module. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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