Transcytosis of IgE-antigen complexes by CD23a in human intestinal epithelial cells and its role in food allergy.
OBJECTIVE
Secreted immunoglobulins play an integral role in host defense at mucosal surfaces, and recent evidence shows that IgG can participate in antigen sampling from the intestinal lumen. We examined whether IgE also could facilitate transepithelial antigen sampling.


METHODS
Stool samples from food-allergic patients undergoing oral food challenge were analyzed for CD23 and food-specific IgE. CD23 isoform expression on primary human intestinal epithelial cells (IEC) was analyzed by polymerase chain reaction. The role of CD23 isoforms in transcytosis of antigen and IgE-antigen complexes was assessed using polarized human T84 cells retrovirally transfected with CD23a or CD23b.


RESULTS
CD23 was expressed constitutively on IECs, and food-allergic patients had increased levels of soluble CD23 and food-specific IgE in the stool after challenge. CD23a, but not CD23b, was expressed by primary human IECs. We show in transcytosis assays that CD23a, but not CD23b, acts as a bidirectional transporter of IgE. In addition, specific IgE facilitated the uptake of antigen from the apical surface of an epithelial monolayer by diverting antigen from delivery to lysosomes. Finally, delivery of antigen-IgE complexes across the epithelial barrier could induce the degranulation of rat basophil leukemia cells transfected with the human high-affinity IgE receptor.


CONCLUSIONS
These studies show that CD23a is expressed normally on human IECs, and in the presence of IgE can function as an antigen-sampling mechanism capable of activating subepithelial mast cells. IgE may serve as a secretory immunoglobulin that in concert with CD23 participates in food-induced pathophysiology of the gastrointestinal tract.
Li
Hongxing
H
Department of Medicine/Division of Clinical Immunology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Nowak-Wegrzyn
Anna
A
Charlop-Powers
Zachary
Z
Shreffler
Wayne
W
Chehade
Mirna
M
Thomas
Sunil
S
Roda
Giulia
G
Dahan
Stephanie
S
Sperber
Kirk
K
Berin
M Cecilia
MC
D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005243:Feces / Q000737:chemistry; D005512:Food Hypersensitivity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism*; D007408:Intestinal Absorption / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E