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Immunity. 2015 Mar 17;42(3):512-23. doi: 10.1016/j.immuni.2015.02.004. Epub 2015 Mar 10.

Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy.

Author information

1
Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
2
Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
3
Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA.
4
Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: talal.chatila@childrens.harvard.edu.

Abstract

Oral immunotherapy has had limited success in establishing tolerance in food allergy, reflecting failure to elicit an effective regulatory T (Treg) cell response. We show that disease-susceptible (Il4ra(F709)) mice with enhanced interleukin-4 receptor (IL-4R) signaling exhibited STAT6-dependent impaired generation and function of mucosal allergen-specific Treg cells. This failure was associated with the acquisition by Treg cells of a T helper 2 (Th2)-cell-like phenotype, also found in peripheral-blood allergen-specific Treg cells of food-allergic children. Selective augmentation of IL-4R signaling in Treg cells induced their reprogramming into Th2-like cells and disease susceptibility, whereas Treg-cell-lineage-specific deletion of Il4 and Il13 was protective. IL-4R signaling impaired the capacity of Treg cells to suppress mast cell activation and expansion, which in turn drove Th2 cell reprogramming of Treg cells. Interruption of Th2 cell reprogramming of Treg cells might thus provide candidate therapeutic strategies in food allergy.

PMID:
25769611
PMCID:
PMC4366316
DOI:
10.1016/j.immuni.2015.02.004
[Indexed for MEDLINE]
Free PMC Article

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