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T Cell Intrinsic Responses to TGFβ Regulates Allergen Sensitization By Modulating Type 2 T Follicular Helper Cell Development

ABSTRACT: Immunoglobulin E (IgE) is a potent mediator of allergic diseases, but the mechanisms that regulate IgE responses to innocuous environmental and food antigens remain unclear. Patients with Loeys-Dietz syndrome (LDS) who have mutations in genes encoding the TGFβ receptor are predisposed to IgE-mediated disorders. Here, using patient samples and a mouse model, we demonstrate that LDS mutations lead to reduced canonical TGFβ signaling, elevated total and allergen-specific IgE, increased type 2 follicular helper T cells (Tfh2), and exaggerated germinal center activity that was not prevented by the presence of wild type T regulatory cells. T cell intrinsic defects in LDS mice resulted in spontaneous sensitization to orally administered OVA, and inhibition of mammalian target of rapamycin (mTOR) prevented the exaggerated Tfh and IgE responses to OVA. Thus, TGFβ limits human and mouse Tfh2 cell development via the phosphatidylinositol-3-OH kinase gamma (PI3Kg)/AKT/mTOR pathway, and disruption of this pathway promotes allergic inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE203379 | GEO | 2023/08/01

REPOSITORIES: GEO

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T Cell Intrinsic Responses to TGFβ Regulates Allergen Sensitization By Modulating Type 2 T Follicular Helper Cell Development

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