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

Natalia Torow; Ronghui Li; Thomas Charles Adrian Hitch; Clemens Mingels; Shahed Al Bounny; Niels van Best; Eva-Lena Stange; Britta Simons; Tiago Maie; Lennart Ruettger; Narasimha Murthy Keshava Prasad Gubbi; Darryl Adelaide Abbott; Adam Benabid; Michael Gadermayr; Solveig Runge; Nicole Treichel; Dorit Merhof; Stephan Patrick Rosshart; Nico Jehmlich; Timothy Wesley Hand; Martin von Bergen; Felix Heymann; Oliver Pabst; Thomas Clavel; Frank Tacke; Hugues Lelouard; Ivan Gesteira Costa; Mathias Walter Hornef

doi:10.1016/j.immuni.2023.04.002

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

Natalia Torow^*, Ronghui Li, Thomas Charles Adrian Hitch, Clemens Mingels, Shahed Al Bounny, Niels van Best, Eva-Lena Stange, Britta Simons, Tiago Maie, Lennart Ruettger, Narasimha Murthy Keshava Prasad Gubbi, Darryl Adelaide Abbott, Adam Benabid, Michael Gadermayr, Solveig Runge, Nicole Treichel, Dorit Merhof, Stephan Patrick Rosshart, Nico Jehmlich, Timothy Wesley HandMartin von Bergen, Felix Heymann, Oliver Pabst, Thomas Clavel, Frank Tacke, Hugues Lelouard, Ivan Gesteira Costa, Mathias Walter Hornef^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 sig-nificant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, sub-sequently 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.

Original language	English
Pages (from-to)	1220-1238.e7
Number of pages	27
Journal	Immunity
Volume	56
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2023.04.002
Publication status	Published - 13 Jun 2023

Keywords

DENDRITIC CELLS
GUT MICROBIOTA
EARLY-LIFE
DIARRHEAL DISEASE
RESPONSES
MOUSE
HOMEOSTASIS
INDUCTION
ALPHA
COLONIZATION

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Cite this

Torow, N., Li, R., Hitch, T. C. A., Mingels, C., Al Bounny, S., van Best, N., Stange, E.-L., Simons, B., Maie, T., Ruettger, L., Gubbi, N. M. K. P., Abbott, D. A., Benabid, A., Gadermayr, M., Runge, S., Treichel, N., Merhof, D., Rosshart, S. P., Jehmlich, N., ... Hornef, M. W. (2023). M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer's patch. Immunity, 56(6), 1220-1238.e7. https://doi.org/10.1016/j.immuni.2023.04.002

@article{0fb6b8f39da843c894d36ce90e3b5afb,

title = "M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer's patch",

abstract = "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 sig-nificant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, sub-sequently 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.",

keywords = "DENDRITIC CELLS, GUT MICROBIOTA, EARLY-LIFE, DIARRHEAL DISEASE, RESPONSES, MOUSE, HOMEOSTASIS, INDUCTION, ALPHA, COLONIZATION",

author = "Natalia Torow and Ronghui Li and Hitch, {Thomas Charles Adrian} and Clemens Mingels and {Al Bounny}, Shahed and {van Best}, Niels and Eva-Lena Stange and Britta Simons and Tiago Maie and Lennart Ruettger and Gubbi, {Narasimha Murthy Keshava Prasad} and Abbott, {Darryl Adelaide} and Adam Benabid and Michael Gadermayr and Solveig Runge and Nicole Treichel and Dorit Merhof and Rosshart, {Stephan Patrick} and Nico Jehmlich and Hand, {Timothy Wesley} and {von Bergen}, Martin and Felix Heymann and Oliver Pabst and Thomas Clavel and Frank Tacke and Hugues Lelouard and Costa, {Ivan Gesteira} and Hornef, {Mathias Walter}",

year = "2023",

month = jun,

day = "13",

doi = "10.1016/j.immuni.2023.04.002",

language = "English",

volume = "56",

pages = "1220--1238.e7",

journal = "Immunity",

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publisher = "Cell Press",

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Torow, N, Li, R, Hitch, TCA, Mingels, C, Al Bounny, S, van Best, N, Stange, E-L, Simons, B, Maie, T, Ruettger, L, Gubbi, NMKP, Abbott, DA, Benabid, A, Gadermayr, M, Runge, S, Treichel, N, Merhof, D, Rosshart, SP, Jehmlich, N, Hand, TW, von Bergen, M, Heymann, F, Pabst, O, Clavel, T, Tacke, F, Lelouard, H, Costa, IG & Hornef, MW 2023, 'M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer's patch', Immunity, vol. 56, no. 6, pp. 1220-1238.e7. https://doi.org/10.1016/j.immuni.2023.04.002

TY - JOUR

T1 - M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer's patch

AU - Torow, Natalia

AU - Li, Ronghui

AU - Hitch, Thomas Charles Adrian

AU - Mingels, Clemens

AU - Al Bounny, Shahed

AU - van Best, Niels

AU - Stange, Eva-Lena

AU - Simons, Britta

AU - Maie, Tiago

AU - Ruettger, Lennart

AU - Gubbi, Narasimha Murthy Keshava Prasad

AU - Abbott, Darryl Adelaide

AU - Benabid, Adam

AU - Gadermayr, Michael

AU - Runge, Solveig

AU - Treichel, Nicole

AU - Merhof, Dorit

AU - Rosshart, Stephan Patrick

AU - Jehmlich, Nico

AU - Hand, Timothy Wesley

AU - von Bergen, Martin

AU - Heymann, Felix

AU - Pabst, Oliver

AU - Clavel, Thomas

AU - Tacke, Frank

AU - Lelouard, Hugues

AU - Costa, Ivan Gesteira

AU - Hornef, Mathias Walter

PY - 2023/6/13

Y1 - 2023/6/13

N2 - 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 sig-nificant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, sub-sequently 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.

AB - 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 sig-nificant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, sub-sequently 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.

KW - DENDRITIC CELLS

KW - GUT MICROBIOTA

KW - EARLY-LIFE

KW - DIARRHEAL DISEASE

KW - RESPONSES

KW - MOUSE

KW - HOMEOSTASIS

KW - INDUCTION

KW - ALPHA

KW - COLONIZATION

U2 - 10.1016/j.immuni.2023.04.002

DO - 10.1016/j.immuni.2023.04.002

M3 - Article

C2 - 37130522

SN - 1074-7613

VL - 56

SP - 1220-1238.e7

JO - Immunity

JF - Immunity

IS - 6

ER -