Antigen targeting to MHC class II-enriched late endosomes in colonic epithelial cells: trafficking of luminal antigens studied in vivo in Crohn's colitis patients.
In Crohn's disease (CD), colonic epithelial cells (CECs) are suggested to stimulate pro-inflammatory CD4+ T cells. However, the endocytic pathways of luminal antigens involved in underlying MHC class II presentation by CECs remain unknown. Our aim was to elucidate antigen trafficking and associated MHC class II expression in CECs of CD patients in vivo. In CD patients (Crohn's colitis and remission) and healthy controls undergoing colonoscopy, ovalbumin (OVA) was sprayed onto inflamed or healthy mucosa. The subcellular localization of OVA and MHC class II was visualized in biopsies taken from OVA-incubated mucosa using fluorescence and cryoelectron microscopy. Targeting of OVA into late endosomes of CECs was found in healthy (controls and CD in remission) and inflamed mucosa (Crohn's colitis). MHC class II expression in CECs was not detected in healthy mucosa but strongly up-regulated during CD inflammation. Induced MHC class II in CECs was predominantly seen at basolateral membranes and in late endosomes, which were efficiently accessed by internalized OVA. Our data provide in vivo evidence that the endocytic pathway of luminal antigens in CECs of Crohn's colitis patients intersects MHC class II-enriched late endosomes and support the postulated role of CECs in MHC class II-associated antigen presentation during CD.
Büning
Jürgen
J
Medizinische Klinik I and Institut für Anatomie, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany. buening@anat.uni-luebeck.de
Hundorfean
Gheorghe
G
Schmitz
Martina
M
Zimmer
Klaus-Peter
KP
Strobel
Stephan
S
Gebert
Andreas
A
Ludwig
Diether
D
D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000166:cytology* / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010047:Ovalbumin / Q000378:metabolism*; D021381:Protein Transport
D000941:Antigens; D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin