TIM-4 Expressed by Mucosal Dendritic Cells Plays a Critical Role in Food Antigen–Specific Th2 Differentiation and Intestinal Allergy

Yang, Ping‐Chang; Xing, Zhou; Berin, M. Cecilia; Söderholm, Johan D.; Feng, Bai–Sui; Wu, Linda; Yeh, Chuan-Sung

doi:10.1053/j.gastro.2007.08.006

Cited by 128 publications

(179 citation statements)

References 23 publications

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“…The interaction of TIM-4 and TIM-1 (on T cells) can drive naive CD4 1 T cells to differentiate into Th2 cells. 3,23 In summary, the present data indicate that patients with SEB 1 CRS are prone to FA; the ingested SEB can be degraded to small peptides (Ssp) in the intestine. The Ssps have the properties of haptens to form adducts with macromolecular antigens.…”

Section: Discussionmentioning

confidence: 60%

“…SEB may be ingested into the digestive tract via contaminated food, or mixing in the discharge of rhinosinusitis to be swallowed down to the gastrointestinal tract. Our previous studies 3,16 indicate that concurrent exposure to SEB and food antigen can induce the skewed antigen-specific Th2 inflammation in the intestine, in which T cell immunoglobulin mucin domain (TIM)-4 plays a critical role in the induction of skewed Th2 polarization. 3,23 Others found that mixed SEB and food antigens can compromise the established oral tolerance and induce the food antigen-specific Th2 inflammation in the intestine.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies 3,16 indicate that concurrent exposure to SEB and food antigen can induce the skewed antigen-specific Th2 inflammation in the intestine, in which T cell immunoglobulin mucin domain (TIM)-4 plays a critical role in the induction of skewed Th2 polarization. 3,23 Others found that mixed SEB and food antigens can compromise the established oral tolerance and induce the food antigen-specific Th2 inflammation in the intestine. 24 In addition, SEB involvement in the pathogenesis of allergic disorders in the airway and skin has been well recognized.…”

Section: Discussionmentioning

confidence: 99%

“…Based on animal model studies, the ingestion of a purified antigen, such as ovalbumin (OVA), generally induces the immune tolerance to the specific antigen, 2 while exposure to a mixture of an antigen and an adjuvant induces sensitization to the specific antigen. 3 Therefore, it seems that the presence or absence of adjuvants is a checkpoint for the induction of immune tolerance or sensitization; the underlying mechanisms have not yet been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…As aforementioned, some bacterial products are used as adjuvants in the establishment of animal models of allergic diseases. 3,7,15 Whether the microbial products act in the same way as hapten is unknown. We previously observed that patients with chronic rhinosinusitis (CRS) and S. aureus infection were prone to suffer from immune disorders in the intestine.…”

Section: Introductionmentioning

confidence: 99%

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Staphylococcal enterotoxin B-derived haptens promote sensitization

Yang

Xiao

et al. 2012

Cell Mol Immunol

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T helper 2 (Th2) polarization is a major pathological feature in allergic diseases; its etiology is not fully understood. This study aims to elucidate the adjuvant effect of the microbial product-derived small peptides in the initiation of antigen-specific Th2 polarization. In this study, a clinical survey of patients with chronic rhinosinusitis (CRS) and food allergy (FA) was carried out. The Staphylococcal enterotoxin B (SEB)-derived small peptides (Ssps) were examined in the human stool extracts. The formation of Ssp/antigen adducts was tested in a protein-protein combination assay. The bone marrow-derived dendritic cells (BMDCs) were employed to test the role of Ssp/ovalbumin (OVA) adducts in the dendritic cell (DC) maturation. A mouse model was developed to test the role of Ssp/OVA adducts in the initiation of Th2 polarization in the intestine. The results showed that 54 (18.2%) patients with FA were diagnosed among 296 patients with SEB 1 CRS; only eight (2.9%) FA patients were identified among 272 patients with SEB 2 CRS. Ssps were detected in the stool protein extracts from FA patients with SEB 1 CRS, but not in those with SEB 2 CRS. Ssp/OVA adducts induced DC maturation, speeded up DC migration, activated CD4 1 T cells in the regional lymph nodes and induced skewed Th2 polarization in the local tissue. We conclude that patients with SEB 1 CRS are prone to suffering from FA. SEB can be degraded to Ssps in the gastrointestinal tract. The Ssps can bind macromolecular antigens to form adducts to promote the antigenicity of the antigens and induction of the antigen-specific Th2 polarization and inflammation in the local tissue.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Staphylococcal enterotoxin B-derived haptens promote sensitization

Yang

Xiao

et al. 2012

Cell Mol Immunol

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Experimental Approaches to the Study of Food Allergy

Berin

Masilamani

2013

Food Allergy

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Survivin facilitates T‐helper 2–biased inflammation in the airway

Xue

Zhao

et al. 2019

Int Forum Allergy Rhinol

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BackgroundThe biased T helper 2 (Th2) responses play a critical role in the pathogenesis of allergy. The underlying mechanism is not fully understood yet. Survivin can regulate multiple cellular activities. This study aims to elucidate the role of survivin in the development and maintenance of Th2 polarization.MethodsCD4+ T cells were isolated from blood samples collected from patients with allergic asthma (AS) and HS control (HS) subjects. Mice carrying CD4+ T cells with survivin knockout (KO mice) were employed to test the role of survivin in the development of the biased Th2 responses.ResultsKO mice failed to induce airway allergy. Peripheral CD4+ T cells expressed survivin, which was higher in the AS group than that in the HS group. Naive CD4+ T cells with higher expression of survivin were prone to differentiating into Th2 cells. Survivin bound to the Il4 promoter in CD4+ T cells to enhance Il4 gene transcription. The expression of Fas was lower in CD4+ T cells of the AS group than that in the HS group. Overexpression of survivin suppressed the expression of Fas and impaired the activation‐induced cell death (AICD) of CD4+ T cells.ConclusionSurvivin facilitates the development of biased Th2 polarization through promoting expression of interleukin 4 (IL‐4) and impairing the AICD machinery of CD4+ T cells. To modulate the expression of survivin in CD4+ T cells has the translational potential in the treatment of allergic diseases.

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TIM-4 Expressed by Mucosal Dendritic Cells Plays a Critical Role in Food Antigen–Specific Th2 Differentiation and Intestinal Allergy

Cited by 128 publications

References 23 publications

Staphylococcal enterotoxin B-derived haptens promote sensitization

Staphylococcal enterotoxin B-derived haptens promote sensitization

Experimental Approaches to the Study of Food Allergy

Survivin facilitates T‐helper 2–biased inflammation in the airway

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