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The clinical signs primarily consist of increased serum IgE levels, eczema, repeated skin infections, allergies, and upper respiratory tract infections. Using CRISPR\/Cas9 technology, we generated a <jats:italic>DOCK8<\/jats:italic> exon 45 mutation in mice, mirroring the mutation found in patients. The results indicated that <jats:italic>DOCK8<\/jats:italic> mutation impairs peripheral T cell homeostasis, disrupts regulatory T cells (Tregs) development, increases ICOS expression in Tregs within peripheral lymph nodes (pLn), and promotes Th17 cell differentiation within the spleen and pLn. Upon virus infection, <jats:italic>DOCK8<\/jats:italic> mutation CD4<jats:sup>+<\/jats:sup> T cells have a Th2 effector fate. RNA\u2010bulk sequencing data revealed alternations in the mTOR pathway of <jats:italic>DOCK8<\/jats:italic> mutant CD4<jats:sup>+<\/jats:sup> T cells. We observed that <jats:italic>DOCK8<\/jats:italic> mutation upregulates the glycolysis levels in CD4<jats:sup>+<\/jats:sup> T cells, which is related to the Akt\/mTOR\/S6\/HIF\u20101\u03b1 pathway. In summary, our research elucidates that DOCK8 regulates the differentiation of helper T cells by modulating the glycolytic pathway in CD4<jats:sup>+<\/jats:sup> T cells, thereby advancing the comprehension and offering potential treatment of diseases in DOCK8\u2010deficient patients.<\/jats:p>","DOI":"10.1002\/mco2.747","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T05:01:37Z","timestamp":1727326897000},"source":"Crossref","is-referenced-by-count":6,"title":["Dedicator of cytokinesis 8 (DOCK8) mutation impairs the differentiation of helper T cells by regulating the glycolytic pathway of CD4<sup>+<\/sup> T cells"],"prefix":"10.1002","volume":"5","author":[{"given":"Panpan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Huazhong University of Science and Technology  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