Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3

Ostroukhova, Marina; Seguin-Devaux, Carole; Oriss, Timothy B.; Dixon-McCarthy, Barbara; Yang, Liyan; Ameredes, Bill T.; Corcoran, Timothy E.; Ray, Anuradha

doi:10.1172/jci20509

Cited by 155 publications

(136 citation statements)

References 55 publications

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“…Overexpression of TGF-β in OVA-specific CD4+ cells abolished the airway hyperresponsiveness and airway inflammation induced by OVA-specific Th2 cells in a murine model of allergic asthma [32]. Administration of anti-TGF-β antibody to sensitized mice before the transfer of CD4+ CD25+ T regulatory cells countered the suppressor effect of these cells on allergen-induced airway hyperresponsiveness [33], corroborating previous reports in which soluble and membrane-bound TGF-β is involved in airway tolerance induced by CD4+ T cells [34]. We demonstrated that the oral administration of GMP prior to and during sensitization increases the production of TGF-β by splenocytes in response to allergens, indicating that this cytokine may be participating in the immunoregulatory activity of GMP in allergy.…”

Section: Discussionsupporting

confidence: 82%

Novel Mechanisms Underlying the Therapeutic Effect of Glycomacropeptide on Allergy: Change in Gut Microbiota, Upregulation of TGF-β, and Inhibition of Mast Cells

Jiménez¹,

Cervantes‐García²,

Muñoz³

et al. 2016

Int Arch Allergy Immunol

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Background: The prevalence of allergic diseases is globally increasing. We have previously described that glycomacropeptide (GMP), a bioactive milk peptide, has therapeutic value in experimental models of skin hypersensitivity, anaphylaxis, and asthma, as it prevents an excessive T helper type 2 cell immune response. The aim of this study was to analyze the effect of GMP on key elements directly involved in the development or control of allergy, in order to improve the precise knowledge about its mechanism of action. Methods: Rats were systemically sensitized with ovalbumin and orally treated with GMP. Levels of Lactobacillus, Bifidobacterium, and Bacteroides were analyzed in their feces. Splenocytes were isolated and the production of transforming growth factor (TGF)-β by allergens was measured. Intradermal skin reactions were developed to evaluate in vivo activation of mast cells. Peritoneal mast cells were isolated and activated by the allergen, and histamine secretion was determined. Results: GMP administration increased the amount of intestinal Lactobacillus and Bifidobacterium of allergen-sensitized animals after 3 days of treatment. The increase in Bacteroides was also significant, but only after 17 days of GMP administration. Ten days after treatment cessation, Lactobacillus and Bacteroides were still elevated. GMP intake also elevated the production of TGF-β in the splenocytes of sensitized animals. In addition, treatment with GMP attenuated mast cell activation by the allergen and inhibited histamine secretion, without affecting the number of mast cells. Conclusions: The prebiotic action of GMP on allergy-protective microbiota, an increase in TGF-β production, and a reduction in mast cell response to allergens are novel mechanisms that explain the antiallergic activity of GMP.

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Section: Discussionsupporting

confidence: 82%

Novel Mechanisms Underlying the Therapeutic Effect of Glycomacropeptide on Allergy: Change in Gut Microbiota, Upregulation of TGF-β, and Inhibition of Mast Cells

Jiménez¹,

Cervantes‐García²,

Muñoz³

et al. 2016

Int Arch Allergy Immunol

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“…CD25 -T cells into lymphopenic Rag -/-or scid mice [54,55]. In addition to the IBD model, IL-10 and TGF-b have been shown to play an important role in Treg-mediated control of allergic immune responses [56,57]. Similarly, both IL-10 and TGF-b appear to be important mediators of Treg function in the cure of, or protection against experimental autoimmune encephalomyelitis (EAE) [58], a mouse model used for the study of human multiple sclerosis (MS).…”

Section: Inhibitory Cytokinesmentioning

confidence: 99%

Regulatory T cells and immune tolerance to tumors

Cao

2009

Immunol Res

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Immune cells infiltrate tumors and make up a significant component of the multicellular cancer micro-environment, yet the immune system often fails to prevent tumor formation and progression. One explanation for this paradox is the presence of tolerance-promoting regulatory T cells (Tregs) that counteract antitumor immune cells. Tregs were known to be essential for maintaining self-tolerance. Recently, Tregs have been found to promote tolerance to tumors in mouse models. Moreover, Treg infiltration in human tumors and malignant ascites is associated with worse clinical outcomes for various types of cancers. As many reviews have discussed the development and function of Tregs, this review focuses on the cellular and molecular mechanisms by which Tregs influence antitumor immune responses, and also discusses how these mechanisms might be exploited to develop innovative immune-based approaches that can improve cancer therapy.

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“…Like IL-10, TGF-β also induces the peripheral expression of the transcription factor Foxp3, promoting the generation of CD4 + CD25 + Tregs that are able to inhibit allergic airway disease [98][99][100]. TGF-β influences the lineage specificity of effector T cell subsets.…”

Section: Fungal Asthma-associated Inflammationmentioning

confidence: 99%

Allergic Inflammation in Aspergillus fumigatus-Induced Fungal Asthma

Ghosh

Hoselton

Schuh

2015

Curr Allergy Asthma Rep

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Although fungi are pervasive in many environments, few cause disease in humans. Of these, Aspergillus fumigatus is particularly well suited to be a pathogen of the human lung. Its physical and biological characteristics combine to provide an organism that can cause tremendous morbidity and high mortality if left unchecked. Luckily, that is rarely the case. However, repeated exposure to inhaled A. fumigatus spores often results in an immune response that carries significant immunopathology, exacerbating asthma and changing the structure of the lung with chronic impacts to pulmonary function. This review focuses on the current understanding of the mechanisms that are associated with fungal exposure, sensitization, and infection in asthmatics, as well as the function of various inflammatory cells associated with severe asthma with fungal sensitization.

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Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3

Cited by 155 publications

References 55 publications

Novel Mechanisms Underlying the Therapeutic Effect of Glycomacropeptide on Allergy: Change in Gut Microbiota, Upregulation of TGF-β, and Inhibition of Mast Cells

Novel Mechanisms Underlying the Therapeutic Effect of Glycomacropeptide on Allergy: Change in Gut Microbiota, Upregulation of TGF-β, and Inhibition of Mast Cells

Regulatory T cells and immune tolerance to tumors

Allergic Inflammation in Aspergillus fumigatus-Induced Fungal Asthma

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