c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium.
M cells reside within the follicle-associated epithelium (FAE) overlying the gut-associated lymphoid tissues. These unique phagocytic epithelial cells enable the mucosal immune system to sample antigens within the lumen of the intestine. The differentiation of M cells from uncommitted precursors in the FAE is dependent on the production of receptor activator of nuclear factor-κB ligand (RANKL) by subepithelial stromal cells. The ligation of a variety of cell surface receptors activates the nuclear factor-κB (NF-κB) family of transcription factors which in-turn induce the transcription of multiple target genes. RANKL-stimulation can stimulate the nuclear translocation of the NF-κB subunit c-Rel. We therefore used c-Rel-deficient mice to determine whether the differentiation and functional maturation of M cells in the Peyer's patches was dependent on c-Rel. Our data show that c-Rel-deficiency does not influence the expression of RANKL or RANK in Peyer's patches, or the induction of M-cell differentiation in the FAE. RANKL-stimulation in the differentiating M cells induces the expression of SpiB which is essential for their subsequent maturation. However, SpiB expression in the FAE was also unaffected in the absence of c-Rel. As a consequence, the functional maturation of M cells was not impaired in the Peyer's patches of c-Rel-deficient mice. Although our data showed that the specific expression of CCL20 and ubiquitin D in the FAE was not impeded in the absence of c-Rel, the expression of ubiquitin D was dramatically reduced in the B cell-follicles of c-Rel-deficient mice. Coincident with this, we also observed that the status of follicular dendritic cells in the B cell-follicles was dramatically reduced in Peyer's patches from c-Rel-deficient mice. Taken together, our data show that c-Rel is dispensable for the RANKL-mediated differentiation and functional maturation of M cells.
The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
Anuj
A
Sehgal
Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Atsushi
A
Kobayashi
The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
David S
DS
Donaldson
The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. Electronic address: neil.mabbott@roslin.ed.ac.uk.
Neil A
NA
Mabbott
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D010581:Peyer's Patches / Q000166:cytology* / Q000502:physiology*; D010641:Phenotype; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics* / Q000378:metabolism*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D057900:Transcytosis / Q000235:genetics / Q000276:immunology
D015415:Biomarkers; D020569:Proto-Oncogene Proteins c-rel; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
Follicle-associated epithelium; M cells; Peyer’s patches; RANKL; c-Rel
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