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* Laboratoire des Interactions Lympho-Epithéliales, Département de Biologie Cellulaire et Infection, Institut Pasteur,
Institut National de la Santé et de la Recherche Médical, Unité 478, Faculté de Médecine Xavier Bichat, and
Institut National de la Santé et de la Recherche Médical, Institut Cochin Centre National de la Recherche Scientifque et Université René Descartes, Paris, France
In the intestine, the follicle-associated epithelium (FAE) of
Peyers patches (PP) performs Ag sampling as the first step in
developing immune responses. Depending on the species, this epithelium
contains 1050% of M cells, which act as regulated gates in
epithelial barriers that can be used opportunistically by pathogens to
invade their host. However, the mechanisms involved in the
differentiation and uptake processes of M cells are not known, in part
because their limited number in the intestinal mucosa has hampered
molecular and biochemical studies. In this work we provide evidence
that PP lymphocytes can themselves modulate gene expression in PP in
vivo and in an in vitro model of FAE. Transgenic mice carrying a
reporter gene under the control of a modified L-pyruvate
kinase promoter (SVPK) exhibit strong transgene expression in PP and
FAE, but not in the adjacent villous cells. We used the mouse
intestinal epithelial cell line m-ICcl2 transfected with
the SVPK promoter fused to
-galactosidase to investigate the direct
effect of PP lymphocytes on SVPK promoter activity.
-Galactosidase
expression was 4.4-fold higher in transfected m-ICcl2 cells
when they were cultured with PP lymphocytes. Conversely, green
fluorescent protein expression was 1.8-fold lower in stably transfected
differentiated intestinal Caco-2cl1 cells with the sucrase
isomaltase promoter fused to green fluorescent protein cDNA when they
were cultured with PP lymphocytes, indicating that the in vivo FAE
down-regulation of sucrase isomaltase promoter is transcriptionally
regulated.
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