Interactions between stem cell factor and c-Kit are required for intestinal immune system homeostasis.
Interactions between stem cell factor (SCF) and its receptor, c-Kit, are important for development of hematopoietic, melanocytes, and germ cells. T lymphocytes appeared normal in c-Kit (W/Wv) or SCF (SI/SId) mutant mice, except for those residing within the intestinal epithelium, the intraepithelial lymphocytes (IEL). Normally, IEL are composed of equal numbers of cells with alpha beta or gamma delta T cell receptors. In mutant mice, beginning at 6-8 weeks of age, the number of gamma delta IEL decreased, whereas alpha beta IEL increased. The latter was due largely to an increased CD4+ CD8+ TCR alpha beta subset, suggesting that these cells may be intermediates in the alpha beta IEL lineage. c-Kit or SCF was expressed by IEL or intestinal epithelial cells, respectively, indicating a potential for direct intercellular interaction. This possibility was supported by reconstitution studies that demonstrated that c-Kit mutations directly affected IEL. Thus, SCF-c-Kit interactions are important for homeostasis of the intestinal immune compartment.
Puddington
L
L
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Olson
S
S
Lefrançois
L
L
D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007107:Immune System; D007413:Intestinal Mucosa / Q000276:immunology; D007422:Intestines / Q000276:immunology*; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019089:Stem Cell Factor; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018076:DNA, Complementary; D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases