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TGF?1 mimetic peptide modulates immune response to grass pollen allergens in mice.


ABSTRACT:

Background

Transforming growth factor ?1 (TGF?1) is a cytokine that exerts immunosuppressive functions, as reflected by its ability to induce regulatory T (Treg) cell differentiation and inhibit Th1 and Th2 responses. Hence, peptides that mimic the active core domain of TGF?1 may be promising candidates for modulation of the allergic response. This study aimed to investigate a synthetic TGF?1 mimetic peptide (TGF?1-mim) for its ability to modulate the immune response during allergic sensitization to grass pollen allergens.

Methods

The in vitro action of TGF?1-mim was evaluated in human lung epithelial cells, Jurkat cells, and rat basophilic leukemia cells. The in vivo action was evaluated in a murine model of Phl p 5 allergic sensitization. Additionally, the Th2 modulatory response was evaluated in IL-4 reporter mice.

Results

In vitro, TGF?1-mim downregulated TNF-? production, IL-8 gene expression, and cytokine secretion, upregulated IL-10 secretion, and inhibited Phl p 5-induced basophil degranulation. During Phl p 5 sensitization in mice, TGF?1-mim downregulated IL-2, IL-4, IL-5, IL-13, and IFN-?, upregulated IL-10, and induced Treg cell production. Furthermore, mice treated with TGF?1-mim had lower levels of IgE, IgG1, IgG2a and higher levels of IgA antibodies than control mice. In a reporter mouse, the mimetic inhibited Th2 polarization.

Conclusion

The TGF?1-mim efficiently modulated various important events that exacerbate the allergic microenvironment, including the production of main cytokines that promote Th1 and Th2 differentiation, and the induction of allergen-specific regulatory T cells, highlighting its potential use in therapeutic approaches to modulate the immune response toward environmental allergens.

SUBMITTER: Araujo GR 

PROVIDER: S-EPMC7217028 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

TGFβ1 mimetic peptide modulates immune response to grass pollen allergens in mice.

Araujo Galber R GR   Aglas Lorenz L   Vaz Emília R ER   Machado Yoan Y   Huber Sara S   Himly Martin M   Duschl Albert A   Goulart Luiz R LR   Ferreira Fatima F  

Allergy 20191212 4


<h4>Background</h4>Transforming growth factor β1 (TGFβ1) is a cytokine that exerts immunosuppressive functions, as reflected by its ability to induce regulatory T (Treg) cell differentiation and inhibit Th1 and Th2 responses. Hence, peptides that mimic the active core domain of TGFβ1 may be promising candidates for modulation of the allergic response. This study aimed to investigate a synthetic TGFβ1 mimetic peptide (TGFβ1-mim) for its ability to modulate the immune response during allergic sens  ...[more]

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