Mechanisms of allergy/immunologyThe amino acid sensor general control nonderepressible 2 (GCN2) controls TH9 cells and allergic airway inflammation
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Mice
GCN2KO mice were obtained from the Jackson Laboratory (Bar Harbor, Me) and then crossed with the C57BL/6J (B6) strain (obtained from Huafukang Bioscience, Beijing, China).24 B6 and recombination-activating gene 2 knockout (Rag2KO) mice were purchased from Beijing University Experimental Animal Center (Beijing, China) and Huafukang Bioscience (Beijing, China), respectively. All mice were bred and maintained under specific pathogen-free conditions in the animal facility of the Institute of
GCN2 is dispensable for differentiation of TH1, TH2, and Treg cells
We first confirmed deletion of GCN2 at both the mRNA and protein levels in CD4+ T cells of GCN2KO mice (see Fig E1 in this article's Online Repository at www.jacionline.org). Then we measured percentages of CD4+ and CD8+ T cells in spleens and peripheral lymph nodes and found there were no differences in the percentages of peripheral T cells between WT and GCN2KO mice in physiologic situations (see Fig E2, A and B, in this article's Online Repository at www.jacionline.org). Meanwhile, GCN2
Discussion
The present study revealed 2 new major findings. First, we demonstrated that deficiency of the amino acid sensor GCN2 selectively inhibits TH9 differentiation and IL-9 production, which leads to less severe allergic inflammation in the allergic airway inflammation mouse model. Second, the attenuated TH9 differentiation in naive GCN2KO CD4+ T cells was predominantly caused by downregulation of the eIF2α–NF-κB–HIF1α pathway and its mediated glycolytic pathway.
CD4+ T cells are an important
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Supported by grants from the National Key Research and Development Program of China (2017YFA0104401 to Y.Z.), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030301 to Y.Z.), the National Natural Science Foundation for General and Key Programs (81530049, U1738111 to Y.Z.), and the China Manned Space Flight Technology Project (TZ-1 to Y.Z.).
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work as first authors.