Age and diet act through distinct isoforms of the class II transactivator gene in mouse intestinal epithelium.
OBJECTIVE
Normal weaning induces class II major histocompatibility complex (Ia) and invariant chain (Ii) expression in the mouse intestinal epithelium. Because the class II transactivator protein (CIITA) induces Ia and Ii in most cell types, we hypothesized that diet-induced expression of these genes was through CIITA.


METHODS
Mouse litters were split and weaned onto an elemental diet or a normal (complex) chow diet. On days 24, 31, and 45, epithelial cells were isolated from small intestine with EDTA, and the RNA was extracted from both wild-type and interferon (IFN)-gamma receptor knockout mice. Messenger RNA (mRNA) was measured by Northern blotting, RNase protection assay, and real-time polymerase chain reaction and Ia localized by immunohistochemistry.


RESULTS
By day 31, CIITA mRNA was induced in the intestinal epithelium of normally weaned wild-type mice, and this mirrored the expression of Ii chain mRNA. Mice weaned onto an elemental diet did not exhibit Ii mRNA or increased CIITA mRNA in the intestinal epithelium by day 31, but low levels of Ii mRNA were detectable by day 45. Of the 3 isoforms of CIITA, weaning onto a complex diet induced only CIITA IV by day 31. Mice deficient in the IFN-gamma receptor expressed Ia in the epithelium and they also accumulated Ii mRNA (at low levels) by day 45, irrespective of diet. CIITA III mRNA accumulation mirrored the dietary-independent changes of Ii mRNA.


CONCLUSIONS
Two mechanisms regulate Ii in the mouse intestinal epithelium: a rapid one, which is diet-induced acting through CIITA IV; and a slower, dietary-independent pathway, acting through CIITA III.
Sanderson
Ian R
IR
Research Centre for Gastroenterology, and Research Centre for Surgery, Institute of Cell and Molecular Science, Barts, England. i.r.sanderson@qmul.ac.uk
Bustin
Stephen A
SA
Dziennis
Suzan
S
Paraszczuk
Joanna
J
Stamm
Demetra S
DS
D000367:Age Factors; D000818:Animals; D004032:Diet; D005260:Female; D005526:Food, Formulated; D007413:Intestinal Mucosa / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D020033:Protein Isoforms; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology; D014886:Weaning
C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D020033:Protein Isoforms; D015534:Trans-Activators