Maturation of the Intestinal Epithelial Barrier in Neonatal Rats Coincides with Decreased FcRn Expression, Replacement of Vacuolated Enterocytes and Changed Blimp-1 Expression

PLoS One. 2016 Oct 13;11(10):e0164775. doi: 10.1371/journal.pone.0164775. eCollection 2016.

Abstract

Background: The intestinal barrier is immature in newborn mammals allowing for transfer of bioactive macromolecules, e.g. protecting antibodies, from mother's milk to the blood circulation and in neonatal rodents lasts until weaning. This passage involves the neonatal-Fc-receptor (FcRn) binding IgG in the proximal and highly endocytic vacuolated enterocytes in the distal immature small intestine (SI). Recent studies have suggested an involvement of the transcription factor B-lymphocyte-induced maturation-protein-1 (Blimp-1) in the regulation of SI maturation in mice. Hence, the objective of the present study was to monitor the development of the intestinal barrier function, in relation to Blimp-1 expression during both natural and precociously induced intestinal maturation in rats.

Results: During the suckling period IgG plasma levels increased, while after gut closure it temporarily decreased. This corresponded to a high expression of FcRn in the proximal SI epithelium and the presence of vacuolated enterocytes in the distal SI. The immature foetal-type epithelium was replaced after weaning or induced precocious maturation, by an adult-type epithelium with FcRnneg cells in the proximal and by non-vacuolated enterocytes in the distal SI. In parallel to this epithelial shift, Blimp-1 expression decreased in the distal SI.

Conclusion: The switch from foetal- to adult-type epithelium, with decreased proximal expression of FcRn and distal replacement of vacuolated enterocytes, was concurrent in the two SI regions and could be used for monitoring SI maturation in the rat. The changes in expression of Blimp-1 in the distal SI epithelium followed the maturation pattern.

MeSH terms

  • Animals
  • Animals, Newborn
  • Enterocytes / metabolism*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Immunoglobulin G / blood
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Fc / genetics
  • Receptors, Fc / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • Repressor Proteins / metabolism*

Substances

  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • RNA, Messenger
  • Receptors, Fc
  • Repressor Proteins
  • Fc receptor, neonatal

Grants and funding

This work was supported by grants from the Royal Physiographic Society in Lund (www.fysiografen.se), 2012 and 2013 (EAS), and Director Albert Påhlsson Foundation in Malmö (www.pahlssonsstiftelse.se) (OP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.