Bcl2L12 plays a critical role in the development of intestinal allergy

The skewed T helper (Th) 2 response plays a central role in the pathogenesis of allergic diseases, while its initiating factors remain elusive. Recent studies indicate that Bcl2 like protein-12 (Bcl2L12) is associated with the Th2-biased inflammation. This study is designed to test a hypothesis that Bcl2L12 plays a critical role in the initiation of allergic response. In this study, peripheral CD4⁺ T cells were isolated from food allergy (FA) patients and healthy subjects; A mouse FA model was developed to test the role of Bcl2L12 in induction of allergic response in the intestine. The results showed that expression of Bcl2L12 by CD4⁺ T cells was higher in FA patients and FA mice and positively correlated with expression of Th2 cytokines. CD4⁺ T cells from FA patients showed a Bcl2L12-dependent tendency to differentiate into Th2 cells. Bcl2L12 played a crucial role in induction of allergic response in the intestine. Physical contact between Bcl2L12 and GATA3 facilitated GATA3 to bind Il4 promoter to promote expression of IL-4. Adoptive transfer with Bcl2L12-deficient CD4⁺ T cells to Rag2¯^/¯ mice did not reconstitute the efficient CD4⁺ T cell response as the mice could not be induced FA, while Rag2¯^/¯ mice received WT CD4⁺ T cell transfer were induced FA. In conclusion, Bcl2L12 plays a crucial role in the induction of Th2 polarization and allergic response in the intestine. The Bcl2L12 in CD4⁺ T cells may be a potential target for the treatment of FA.