Dendritic cells (DCs) patrol tissues and transport antigens to lymph nodes to initiate adaptive immune responses. Within tissues, DCs constitute a complex cell population made of distinct subsets that express different markers and eventually display different functions. How cell-intrinsic programs and tissue-specific cues orchestrate DC diversification is only partially understood. By combining single-cell sequencing and intravital imaging, we here show that DC migration to the small intestine epithelium leads to the generation of an “immature-like” intraepithelial pool of cDC2s. These cells exhibit tolerogenic properties in contrast to lamina propria DCs, which are pro-inflammatory, resembling mature DCs. We further identify the actin motor myosin II and the nutrient-derived metabolite retinoic acid as the cell-intrinsic and -extrinsic cues driving the formation of this intraepithelial pool of cDC2s. Together, these results show that fine-tuning of DC migration controls their functional diversification within tissues.
Keywords: dendritic cells, small intestine, cell migration, epithelium, antigen presentation, T cell activation/anergy
Randrian, Violaine and Rivera, Claudia A. and Chikina, Aleksandra and Richer, Wilfrid and Parigi, Sara M. and Maurin, Mathieu and Goudot, Christel and Krndija, Denis and Czarnewski, Paulo and Baulande, Sylvain and Lameiras, Sonia and Helft, Julie and Guermonprez, Pierre and Moreau, Hélène D. and Vignjevic, Danijela Matic and Villablanca, Eduardo J. and Lennon-Duménil, Ana-Maria, Cell Migration Promotes the Functional Diversification of Gut Dendritic Cells (November 5, 2019). Available at SSRN: https://ssrn.com/abstract=3499176 or http://dx.doi.org/10.2139/ssrn.3499176
This version of the paper has not been formally peer reviewed.
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