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However, the roles of PDK1 in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation, especially in T follicular helper (Tfh) cell, remain obscure. Here we reported PDK1 intrinsically promotes the Tfh cell differentiation and germinal center responses upon acute infection by using conditional knockout mice. PDK1 deficiency in T cells caused severe defects in both early differentiation and late maintenance of Tfh cells. The expression of key Tfh regulators was remarkably downregulated in PDK1-deficient Tfh cells, including\n                    <jats:italic>Tcf7<\/jats:italic>\n                    ,\n                    <jats:italic>Bcl6<\/jats:italic>\n                    ,\n                    <jats:italic>Icos<\/jats:italic>\n                    , and\n                    <jats:italic>Cxcr5<\/jats:italic>\n                    . Mechanistically, ablation of PDK1 led to impaired phosphorylation of AKT and defective activation of mTORC1, resulting in substantially reduced expression of Hif1\u03b1 and p-STAT3. Meanwhile, decreased p-AKT also suppresses mTORC2-associated GSK3\u03b2 activity in PDK1-deficient Tfh cells. These integrated effects contributed to the dramatical reduced expression of TCF1 and ultimately impaired the Tfh cell differentiation.\n                  <\/jats:p>","DOI":"10.7554\/elife.61406","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T20:17:36Z","timestamp":1613506656000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.61406","source":"Crossref","is-referenced-by-count":24,"title":["The kinase PDK1 is critical for promoting T follicular helper cell differentiation"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5380-6831","authenticated-orcid":true,"given":"Zhen","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-2443","authenticated-orcid":true,"given":"Yingpeng","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghao","family":"You","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 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