Sp. Colgan et al., Ligation of intestinal epithelial CD1d induces bioactive IL-10: Critical role of the cytoplasmic tail in autocrine signaling, P NAS US, 96(24), 1999, pp. 13938-13943
Citations number
51
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The intestinal epithelium is anatomically positioned to serve as the critic
al interface between the lumen and the mucosal immune system. In addition t
o MHC class I and II antigens, intestinal epithelia constitutively express
the nonclassical MHC molecule CD1d a transmembrane molecule with a short cy
toplasmic tail expressed as a beta(2)-microglobulin-associated 48-kDa glyco
protein and novel beta(2)-microglobulin-independent 37-kDa nonglycosylated
protein on intestinal epithelia. At present, it is not known whether extrac
ellular ligands can signal intestinal epithelial CD1d. To define signaling
of CD Id cytoplasmic tail, retrovirus-mediated gene transfer was used to ge
nerate stable cell lines expressing wild-type CD1d or a chimeric molecule (
extracellular CD1d and cytoplasmic CD1a), and surface CD1d was triggered by
antibody crosslinking. Although wild-type CD1d was readily activated (tyro
sine phosphorylation), no demonstrable signal was evident in cell lines exp
ressing the chimeric molecule. Subsequent studies revealed that anti-Cold c
rosslinking specifically induces epithelial IL-10 mRNA and protein and is b
locked by the tyrosine kinase inhibitor genistein. Further studies addressi
ng epithelial-derived IL-10 revealed that anti-CD1d crosslinking attenuates
IFN-gamma signaling and that such attenuation is reversed by addition of f
unctionally inhibitory IL-10 antibodies. These results define signaling thr
ough surface CD1d, and, importantly, they demonstrate that this pathway may
serve to dampen epithelial proinflammatory signals.