RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium.
Microfold cells (M cells) are specialized epithelial cells situated over Peyer's patches (PP) and other organized mucosal lymphoid tissues that transport commensal bacteria and other particulate Ags into intraepithelial pockets accessed by APCs. The TNF superfamily member receptor activator of NF-kappaB ligand (RANKL) is selectively expressed by subepithelial stromal cells in PP domes. We found that RANKL null mice have <2% of wild-type levels of PP M cells and markedly diminished uptake of 200 nm diameter fluorescent beads. Ab-mediated neutralization of RANKL in adult wild-type mice also eliminated most PP M cells. The M cell deficit in RANKL null mice was corrected by systemic administration of exogenous RANKL. Treatment with RANKL also induced the differentiation of villous M cells on all small intestinal villi with the capacity for avid uptake of Salmonella and Yersinia organisms and fluorescent beads. The RANK receptor for RANKL is expressed by epithelial cells throughout the small intestine. We conclude that availability of RANKL is the critical factor controlling the differentiation of M cells from RANK-expressing intestinal epithelial precursor cells.
Knoop
Kathryn A
KA
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Kumar
Nachiket
N
Butler
Betsy R
BR
Sakthivel
Senthilkumar K
SK
Taylor
Rebekah T
RT
Nochi
Tomonori
T
Akiba
Hisaya
H
Yagita
Hideo
H
Kiyono
Hiroshi
H
Williams
Ifor R
IR
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D005260:Female; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000276:immunology / Q000378:metabolism; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D037121:Plant Lectins / Q000096:biosynthesis / Q000378:metabolism; D053245:RANK Ligand / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000502:physiology; D012485:Salmonella typhi / Q000276:immunology; D039762:Ulex / Q000276:immunology / Q000378:metabolism; D015008:Yersinia enterocolitica / Q000276:immunology
D000941:Antigens; D037121:Plant Lectins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505689:Tnfsf11 protein, mouse; C036850:Ulex europaeus lectins