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

Natalia Torow1, Ronghui Li2, Thomas Charles Adrian Hitch3

  • 1Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen 52074, Germany.

Immunity
|May 2, 2023
PubMed

Insights

Postnatal immune development relies on mononuclear phagocytes (MNPs) in Peyer's patches (PPs). Follicle-associated epithelium (FAE) M cell differentiation drives MNP maturation, crucial for early-life host health.

Area of Science:

  • Immunology
  • Developmental Biology
  • Gastroenterology

Background:

  • Early-life immune system maturation is vital for lifelong health.
  • Mechanisms regulating postnatal immune development remain incompletely understood.
  • Peyer's patches (PPs) are key sites for initiating intestinal immunity.

Purpose of the Study:

  • To investigate the maturation of mononuclear phagocytes (MNPs) in PPs during early life.
  • To identify factors influencing MNP maturation and their impact on T cell priming.
  • To elucidate the role of follicle-associated epithelium (FAE) M cells in immune development.

Main Methods:

  • Analysis of MNP subset composition and distribution in PPs across different postnatal ages.
  • Assessment of MNP maturation markers and CD4+ T cell priming capacity.
  • Investigation of microbial cues and type I interferon (IFN) signaling on MNP maturation.
  • Evaluation of FAE M cell differentiation's role in MNP maturation.

Main Results:

  • Significant age-dependent changes were observed in MNP subsets (cDC1, cDC2, RORgt+ APC) within PPs.
  • Reduced MNP maturation led to impaired CD4+ T cell priming during the postnatal period.
  • Microbial cues and type I IFN signaling partially influenced MNP maturation but were not the primary drivers.
  • FAE M cell differentiation was identified as both necessary and sufficient for driving postweaning MNP maturation.

Conclusions:

  • FAE M cell differentiation is a critical regulator of MNP maturation in PPs.
  • MNP maturation is essential for effective CD4+ T cell priming in early life.
  • Understanding these mechanisms provides insights into optimizing early-life host defense and intestinal immunity.

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