Oral tolerance: Can we make it work?

Ilan, Yaron

doi:10.1016/j.humimm.2009.06.018

Cited by 28 publications

(29 citation statements)

References 134 publications

(239 reference statements)

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“…These cells play different roles that may vary depending on their location and method of antigen presentation. For example, DCs are capable of inducing active T cell immunity via uptake, processing, and presentation of antigen to T cells, but may also induce tolerance by inducing T regulatory cells or deleting T cells (5). DCs may encounter antigen in the gastrointestinal tract by directly sampling luminal contents through dendrites extending to paracellular spaces, by directly interacting with epithelial cells, or by taking up antigen via the Peyer patches.…”

Section: Pathophysiology Of Food Allergymentioning

confidence: 99%

Food allergy

Wang¹,

Sampson²

2011

J. Clin. Invest.

152

117

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Food allergies affect up to 6% of young children and 3%-4% of adults. They encompass a range of disorders that may be IgE and/or non-IgE mediated, including anaphylaxis, pollen food syndrome, food-protein-induced enterocolitis syndrome, food-induced proctocolitis, eosinophilic gastroenteropathies, and atopic dermatitis. Many complex host factors and properties of foods are involved in the development of food allergy. With recent advances in the understanding of how these factors interact, the development of several novel diagnostic and therapeutic strategies is underway and showing promise. Conflict of interest: Hugh A. Sampson is an investor in and paid consultant forAllertein Therapeutics and an investor in Herbal Springs LLC, a holding company for the patents on FAHF-2. Hugh A. Sampson receives research support from the Food Allergy Initiative, a nonprofit foundation supporting food allergy research.

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Section: Pathophysiology Of Food Allergymentioning

confidence: 99%

Food allergy

Wang¹,

Sampson²

2011

J. Clin. Invest.

152

117

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“…De-sensitize disease-triggering antigen Effective in diverse disease models [172][173][174][175] Low; human trials disappointing [184]; too many variables [169] T regulatory cell adoptive transfer…”

Section: Co-stimulatory Signaling Pathways For Immunocyte Activationmentioning

confidence: 99%

“…Immune tolerance to a disease-triggering antigen can be accomplished by ingesting the peptide and relying on the natural immune mechanisms of the intestinal mucosa to adjust to its presence [169,170]. The method is attractive since the treatments lack toxicity, rely on natural mechanisms of mucosal immunity, are easily administered, and promote antigen-specific tolerance.…”

Section: Autoantigen Intolerancementioning

confidence: 99%

Emerging Opportunities for Site-Specific Molecular and Cellular Interventions in Autoimmune Hepatitis

Czaja

2010

Dig Dis Sci

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Current corticosteroid-based treatments of autoimmune hepatitis frequently have incomplete or unsatisfactory outcomes, side effects, and excessive immune suppression. The goal of this review is to describe the advances in developing animal models of autoimmune hepatitis and in treating diverse immune-mediated diseases that make pursuit of site-specific molecular and cellular inventions in autoimmune hepatitis feasible. Prime source and review articles in English were selected by a Medline search through October 2009. A murine model infected with an adenovirus expressing human CYP2D6 is a resource for evaluating new therapies because of its histological and serological features, persistence, and progressive hepatic fibrosis. Synthetic analog peptides that block autoantigen expression, a dimeric recombinant human fusion protein of cytotoxic T lymphocyte antigen-4, monoclonal antibodies against tumor necrosis factor-alpha, recombinant interleukin 10, tolerization techniques for disease-triggering autoantigens, T regulatory cell transfer, vaccination against antigen-specific cytotoxic CD8+ T cells, and gene silencing methods using small inhibitory RNAs are feasible interventions to explore. Treatments directed at dampening immunocyte activation with soluble cytotoxic T lymphocyte antigen-4, inhibiting immunocyte differentiation with recombinant interleukin 10, and improving immunosuppressive activity with regulatory T cell modulation have the most immediate promise. Progress in the development of an animal model of autoimmune hepatitis and experiences in other immune-mediated diseases justify the evaluation of site-specific molecular and cellular interventions in this disease.

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“…Tolerance has been defined as a lack of response to self, but a more appropriate definition of tolerance is 'any mechanism by which a potentially injurious immune response is prevented, suppressed, or shifted to a non-injurious class of immune response' [Weiner, 2004]. Thus, tolerance is related to productive self-recognition, rather than blindness of the immune system to its own components [Ilan, 2009;Weiner, 2004;Shibolet et al 2004a;Safadi et al 2003]. …”

Section: Induction Of Oral Tolerancementioning

confidence: 99%

“…Successful application of oral tolerance for the treatment of human diseases also depends on the strategies used to target the correct cells in the gutliver axis and to improve antigen presentation. The development of immune biomarkers to assess immunologic effects may also assist in the development of this type of immunotherapy [Ilan, 2009;Faria and Weiner, 2005].…”

Section: Effect Of Oral Administration Of Alequel On the Immune Systemmentioning

confidence: 99%

Review: Oral administration of Alequel, a mixture of autologous colon-extracted proteins for the treatment of Crohn’s disease

Israeli

Ilan

2009

Therap Adv Gastroenterol

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The pathogenesis of Crohn's disease involves an immune-mediated damage to the gut mucosa. Current developed therapies are based on the use of immunosuppressive drugs that can lead to significant drug-related adverse responses. There is a need for a therapeutic strategy that is more specific and less global in its effect on the immune system. Oral tolerance is an active process wherein oral administration of antigens is associated with the induction of regulatory cells and the suppression of effector cells directed toward specific and nonspecific antigens. Studies in animal models of experimental colitis suggest that oral administration of proteins extracted from the gut can induce tolerance and alleviate the disease symptoms. Recent clinical trials showed that oral administration of Alequel, an autologous proteincontaining colon extract, to patients with Crohn's disease is safe and may be effective as a therapeutic modality for treating the disease. This treatment was associated with diseaseassociated antigen alterations of the immune response in the patients. Oral administration of Alequel could provide a patient-tailored approach that is side-effect-free for the treatment of patients with Crohn's disease.

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Oral tolerance: Can we make it work?

Cited by 28 publications

References 134 publications

Food allergy

Food allergy

Emerging Opportunities for Site-Specific Molecular and Cellular Interventions in Autoimmune Hepatitis

Review: Oral administration of Alequel, a mixture of autologous colon-extracted proteins for the treatment of Crohn’s disease

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