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Publication : Eosinophils Contribute to Oral Tolerance via Induction of RORγt-Positive Antigen-Presenting Cells and RORγt-Positive Regulatory T Cells.

First Author  Kurihara S Year  2024
Journal  Biomolecules Volume  14
Issue  1 PubMed ID  38254689
Mgi Jnum  J:344624 Mgi Id  MGI:7577541
Doi  10.3390/biom14010089 Citation  Kurihara S, et al. (2024) Eosinophils Contribute to Oral Tolerance via Induction of RORgammat-Positive Antigen-Presenting Cells and RORgammat-Positive Regulatory T Cells. Biomolecules 14(1)
abstractText  Oral tolerance has been defined as the specific suppression of immune responses to an antigen by prior oral administration of the antigen. It has been thought to serve to suppress food allergy. Previous studies have shown that dendritic cells (DCs) and regulatory T cells (Tregs) are involved in the induction of oral tolerance. However, the detailed mechanisms of Treg induction in oral tolerance remain largely unknown. Eosinophils have been recognized as effector cells in allergic diseases, but in recent years, the diverse functions of tissue-resident eosinophils have been reported. Eosinophils in the intestine have been reported to induce Tregs by releasing TGF-beta, but the role of eosinophils in oral tolerance is still controversial. In this study, we analyzed the roles of eosinophils in oral tolerance using eosinophil-deficient DeltadblGATA mice (mice lacking a high-affinity GATA-binding site in the GATA1 promoter). DeltadblGATA mice showed impaired antigen-induced oral tolerance compared to wild-type mice. The induction of RORgammat(+) Tregs in mesenteric lymph nodes (MLNs) by oral tolerance induction was impaired in DeltadblGATA mice compared to wild-type mice. An increase in RORgammat(+) antigen-presenting cells (APCs), which are involved in RORgammat(+) Treg differentiation, in the intestine and MLNs was not seen in DeltadblGATA mice. Notably, the expansion of group 3 innate lymphoid cells (ILC3s), a subset of RORgammat(+) APCs, by oral tolerance induction was seen in wild-type mice but not DeltadblGATA mice. These results suggest that eosinophils are crucial in the induction of oral tolerance, possibly via the induction of RORgammat(+) APCs and RORgammat(+) Tregs.
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