Transcriptional programming of immunoregulatory responses in human Langerhans cells.

Autor:	Davies J; Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Sirvent S; Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Vallejo AF; Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Clayton K; Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Douilhet G; Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Keeler PS; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., West J; Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom., Ardern-Jones M; Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., MacArthur BD; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Singh H; Center for Systems Immunology, Departments of Immunology and Computational and Systems Biology, The University of Pittsburgh, Pittsburgh, PA, United States., Polak ME; Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 20; Vol. 13, pp. 892254. Date of Electronic Publication: 2022 Sep 20 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.892254
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Davies, Sirvent, Vallejo, Clayton, Douilhet, Keeler, West, Ardern-Jones, MacArthur, Singh and Polak.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu