Enhanced transepithelial antigen transport in intestine of allergic mice is mediated by IgE/CD23 and regulated by interleukin-4

Yu, Linda Chia-Hui; Yang, Ping‐Chang; Berin, M. Cecilia; Leo, Vincenza Di; Conrad, Daniel H.; McKay, Derek M.; Satoskar, Abhay R.; Perdue, Mary H.

doi:10.1053/gast.2001.26470

Cited by 100 publications

(91 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In mice, we previously showed that both CD23b and b⌬5 are targeted to the apical membrane of polarized MDCK cells (16), a steady-state localization in agreement with that of CD23 in enterocytes in vivo (26). In contrast, in humans, CD23 has been reported to be localized at both apical and basolateral membranes of intestinal epithelial cells (24).…”

Section: The Cd23a-specific Exon Is Also a Basolateral Targeting Signalmentioning

confidence: 57%

Intracellular Trafficking of CD23: Differential Regulation in Humans and Mice by Both Extracellular and Intracellular Exons

Montagnac

Mollà-Herman

Bouchet

et al. 2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

In mouse models of food allergy, we recently characterized a new CD23b-derived splice form lacking extracellular exon 5, bΔ5, which undergoes constitutive internalization and mediates the transepithelial transport of free IgE, whereas classical CD23b is more efficient in transporting IgE/allergen complexes. These data suggested that regulation of endocytosis plays a central role in CD23 functions and drove us to systematically compare the intracellular trafficking properties of human and murine CD23 splice forms. We found that CD23 species show similar endocytic behaviors in both species; CD23a undergoes constitutive clathrin-dependent internalization, whereas CD23b is stable at the plasma membrane. However, the mechanisms controlling these similar behaviors appeared to be different. In mice, a positive internalization signal was localized in the cytoplasmic region shared by all CD23 splice forms. This positive signal was negatively regulated by the intracellular CD23b-specific exon. In addition, the fact that alternative splice forms lacking exons of the extracellular region (5, 6, 7, and/or 8) were all constitutively internalized suggested that endocytosis of murine CD23 is regulated by a process similar to the outside-in signaling of integrins. In humans, the internalization signal was mapped in the CD23a-specific intracellular exon. Interestingly, this signal also behaved as a basolateral targeting signal in polarized Madin-Darby canine kidney cells. The latter result and the fact that human intestinal cell lines were found to coexpress both CD23a and CD23b provide a molecular explanation for the initial observations that CD23 was found at the basolateral membrane of intestinal epithelial cells from allergic patients.

show abstract

Section: The Cd23a-specific Exon Is Also a Basolateral Targeting Signalmentioning

confidence: 57%

Intracellular Trafficking of CD23: Differential Regulation in Humans and Mice by Both Extracellular and Intracellular Exons

Montagnac

Mollà-Herman

Bouchet

et al. 2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…38 We recently reported that the b isoform of CD23, including some unique splice variants, is expressed on intestinal epithelial cells in sensitized rodents and is up-regulated by IL-4. 34,39 In studies involving blocking antibodies and gene-deficient mice, CD23 was identified as critical for the protected transepithelial transport of IgE-antigen in endosomes. Taken together, our results suggest that the enhanced endosomal transport of antigen in WASsensitized rats was related to elevated CD23 expression on enterocytes induced by IL-4.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 Antigen delivered to the lamina propria then activates mast cells, and released mediators act on epithelial receptors to further increase permeability by loosening intercellular tight junctions (paracellular pathway). Here, we measured HRP flux across the tissue as an indicator of overall transepithelial antigen transport.…”

Section: Transepithelial Antigen Transportmentioning

confidence: 99%

Chronic Psychological Stress in Rats Induces Intestinal Sensitization to Luminal Antigens

Yang

Jury

Söderholm

et al. 2006

The American Journal of Pathology

Self Cite

139

View full text Add to dashboard Cite

There is increasing evidence that stress plays a role in the pathophysiology of chronic intestinal disorders, but the mechanisms remain unclear. Previous studies in rats have revealed that stress decreases gut barrier function and allows excessive uptake of luminal material. Here, we investigated whether chronic psychological stress acts to induce sensitization of intestinal tissues to oral antigens. Rats were subjected to 1 hour per day of water avoidance stress or sham stress daily for 10 days, and horseradish peroxidase (HRP) was delivered by gavage on day 5. Studies to determine sensitization were conducted on day 20. All stressed rats developed HRP-specific IgE antibodies, antigeninduced intestinal secretion, and increased numbers of inflammatory cells in gut mucosa. Luminal HRP was absorbed more readily by enterocytes of stressed animals. In addition, stressed rats had increased expression of interleukin-4 and decreased expression of interferon-␥ in gut mucosa, a cytokine profile that is typical of allergic conditions. Treatment of stressed rats with an antagonist to corticotropin-releasing hormone (previously shown to inhibit stress-enhanced gut permeability) eliminated the manifestations of intestinal hypersensitivity. Our results indicate that the presence of oral antigen during chronic psychological stress alters the immune response (to sensitization rather than oral tolerance) and causes subsequent antigen-induced gut pathophysiology. A number of publications 1-4 in recent years indicate that stress plays a role in gastrointestinal pathophysiology in conditions such as inflammatory bowel disease, irritable bowel syndrome (IBS), and food allergies. In inflammatory bowel disease and perhaps IBS, there is evidence that intestinal tissues may become sensitized to a luminal antigen and that subsequent encounter with the antigen initiates an inflammatory response that is involved in the pathophysiology of disease. [5][6][7][8][9] Although this theory remains controversial, it is clear that sensitization of intestinal tissues is a feature of food allergy. There is little information on the relationship between stress and intestinal anaphylaxis, although several reports indicate that psychological stress triggers allergic reactions in other organ systems.10 -12 With respect to detrimental reactions to oral antigens, immunogenic material must penetrate the intestinal epithelial barrier to contact and activate immune cells in the lamina propria. 13 In a sensitized host, immediate hypersensitivity reactions are initiated by antigen cross-linking of specific IgE antibodies bound to the surface of mucosal mast cells located in close proximity beneath the gut epithelium. Released mediators then act on nearby cells to induce both rapid (within minutes) changes in physiology and delayed (within hours to days) effects. 13,14 In allergic conditions in general, it is not clear how an individual develops sensitivity to a particular antigen. Genetic factors play a role, but persons can develop a hypersensitivity reaction ...

show abstract

“…Several elegant studies have demonstrated a potential function for CD23 to transport IgE and IgE-derived immune complex (IC) across the polarized human intestinal epithelial monolayer (33)(34)(35). Furthermore, the facilitated transport of IgE and uptake of Ags by CD23 are essential steps in the initiation of rapid allergic inflammation in the intestine in a murine model (36,37). All these experiments suggest a role of CD23-mediated IgE transport in food allergies.…”

mentioning

confidence: 99%

CD23-Dependent Transcytosis of IgE and Immune Complex across the Polarized Human Respiratory Epithelial Cells

Palaniyandi

Tomei

et al. 2011

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

IgE-mediated allergic inflammation occurs when allergens cross-link IgE on the surface of immune cells, thereby triggering the release of inflammatory mediators as well as enhancing Ag presentations. IgE is frequently present in airway secretions, and its level can be enhanced in human patients with allergic rhinitis and bronchial asthma. However, it remains completely unknown how IgE appears in the airway secretions. In this study, we show that CD23 (FcεRII) is constitutively expressed in established or primary human airway epithelial cells, and its expression is significantly upregulated when airway epithelial cells were subjected to IL-4 stimulation. In a transcytosis assay, human IgE or IgE-derived immune complex (IC) was transported across a polarized Calu-3 monolayer. Exposure of the Calu-3 monolayer to IL-4 stimulation also enhanced the transcytosis of either human IgE or the IC. A CD23-specific Ab or soluble CD23 significantly reduced the efficiency of IgE or IC transcytosis, suggesting a specific receptor-mediated transport by CD23. Transcytosis of both IgE and the IC was further verified in primary human airway epithelial cell monolayers. Furthermore, the transcytosed Ag–IgE complexes were competent in inducing degranulation of the cultured human mast cells. Because airway epithelial cells are the first cell layer to come into contact with inhaled allergens, our study implies CD23-mediated IgE transcytosis in human airway epithelial cells may play a critical role in initiating and contributing to the perpetuation of airway allergic inflammation.

show abstract

Enhanced transepithelial antigen transport in intestine of allergic mice is mediated by IgE/CD23 and regulated by interleukin-4

Cited by 100 publications

References 35 publications

Intracellular Trafficking of CD23: Differential Regulation in Humans and Mice by Both Extracellular and Intracellular Exons

Intracellular Trafficking of CD23: Differential Regulation in Humans and Mice by Both Extracellular and Intracellular Exons

Chronic Psychological Stress in Rats Induces Intestinal Sensitization to Luminal Antigens

CD23-Dependent Transcytosis of IgE and Immune Complex across the Polarized Human Respiratory Epithelial Cells

Contact Info

Product

Resources

About