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ICOS-mediated inactivation of the FOXO1 transcription factor in the differentiation of T follicular helper cells

ABSTRACT: T follicular helper (Tfh) cells constitute an essential cell type in the induction of antibodies. We report that CD4 T cells lacking Foxo1 almost uniformly became CXCR5int Tfh cells following immunization. Moreover, a Foxo1 loss-of-function complemented an Icos mutation allowing the appearance of Tfh cells along with follicular, class-switched B cells and IgG isotype anti-DNA antibodies. Similarly, FOXO1 deficient Tfh differentiation displayed a substantially reduced dependence on ICOSL. Functional and molecular analyses show that FOXO1 regulates Tfh differentiation through a broad program of gene expression exemplified by positive regulation of Icos and negative regulation of Bcl6. These results demonstrate that a key step in Tfh differentiation is the ICOS-initiated activation of the PI3K-AKT pathway resulting in the inactivation of FOXO1. Performed ChIP-seq analysis to examine the role of foxo1 in the development of Tfh cells

ORGANISM(S): Mus musculus

SUBMITTER: Carol Katayama

PROVIDER: E-GEOD-46525 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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