M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer’s patch

• Published in: Immunity (Cambridge, Mass.) Mass.), 2023-06, Vol.56 (6), p.1220-1238.e7
• Main Authors: Torow, Natalia, Li, Ronghui, Hitch, Thomas Charles Adrian, Mingels, Clemens, Al Bounny, Shahed, van Best, Niels, Stange, Eva-Lena, Simons, Britta, Maié, Tiago, Rüttger, Lennart, Gubbi, Narasimha Murthy Keshava Prasad, Abbott, Darryl Adelaide, Benabid, Adam, Gadermayr, Michael, Runge, Solveig, Treichel, Nicole, Merhof, Dorit, Rosshart, Stephan Patrick, Jehmlich, Nico, Hand, Timothy Wesley, von Bergen, Martin, Heymann, Felix, Pabst, Oliver, Clavel, Thomas, Tacke, Frank, Lelouard, Hugues, Costa, Ivan Gesteira, Hornef, Mathias Walter
• Format: Article
• Language: English
• Subjects: Adaptive immunology; cDC2; Cell Differentiation; dendritic cell; Immunology; Intestinal Mucosa; Intestine, Small; Intestines; Life Sciences; M cell; M Cells; microbiota; neonatal immunology; Peyer's patch; Peyer's Patches; post-natal establishment of intestinal homeostasis; RORgt+ APC
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2023.04.002

Early-life immune development is critical to long-term host health. However, the mechanisms that determine the pace of postnatal immune maturation are not fully resolved. Here, we analyzed mononuclear phagocytes (MNPs) in small intestinal Peyer’s patches (PPs), the primary inductive site of intestinal immunity. Conventional type 1 and 2 dendritic cells (cDC1 and cDC2) and RORgt+ antigen-presenting cells (RORgt+ APC) exhibited significant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, subsequently resulting in a lack in CD4+ T cell priming during the postnatal period. Microbial cues contributed but could not fully explain the discrepancies in MNP maturation. Type I interferon (IFN) accelerated MNP maturation but IFN signaling did not represent the physiological stimulus. Instead, follicle-associated epithelium (FAE) M cell differentiation was required and sufficient to drive postweaning PP MNP maturation. Together, our results highlight the role of FAE M cell differentiation and MNP maturation in postnatal immune development. [Display omitted] •Peyer’s patch (PP) CD4+ T cells exhibit delayed maturation after birth•cDC1 and RORgt+ APC are increased whereas cDC2 are diminished in the neonatal PP•PP APCs exhibit halted maturation and cDC2 show reduced T cell priming capacity•M cell development is required and sufficient to drive APC maturation Despite the critical importance of immune development in early life, our mechanistic understanding of this process is limited. Torow et al. demonstrate that postnatal establishment of intestinal microbe-host interaction is not expressly driven by early microbial colonization, but rather the maturation of Peyer’s patch M cells and antigen-presenting cells.