Interactions between stem cell factor and c-Kit are required for intestinal immune system homeostasis

Immunity. 1994 Dec;1(9):733-9. doi: 10.1016/s1074-7613(94)80015-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • DNA, Complementary
  • Hematopoietic Cell Growth Factors / genetics
  • Hematopoietic Cell Growth Factors / immunology
  • Hematopoietic Cell Growth Factors / metabolism*
  • Immune System
  • Intestinal Mucosa / immunology
  • Intestines / immunology*
  • Leukocyte Count
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-kit
  • RNA, Messenger
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Colony-Stimulating Factor / genetics
  • Receptors, Colony-Stimulating Factor / immunology
  • Receptors, Colony-Stimulating Factor / metabolism*
  • Stem Cell Factor
  • T-Lymphocyte Subsets / immunology*

Substances

  • DNA, Complementary
  • Hematopoietic Cell Growth Factors
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Colony-Stimulating Factor
  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases