@article{361e4a839f824191b6d21d903cbbb967,
title = "The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells",
abstract = "CD4+ follicular helper T cells (T FH cells) are essential for germinal center (GC) responses and long-lived antibody responses. Here we report that naive CD4+ T cells deficient in the transcription factor Foxp1 'preferentially' differentiated into T FH cells, which resulted in substantially enhanced GC and antibody responses. We found that Foxp1 used both constitutive Foxp1A and Foxp1D induced by stimulation of the T cell antigen receptor (TCR) to inhibit the generation of T FH cells. Mechanistically, Foxp1 directly and negatively regulated interleukin 21 (IL-21); Foxp1 also dampened expression of the costimulatory molecule ICOS and its downstream signaling at early stages of T cell activation, which rendered Foxp1-deficient CD4+ T cells partially resistant to blockade of the ICOS ligand (ICOSL) during T FH cell development. Our findings demonstrate that Foxp1 is a critical negative regulator of T FH cell differentiation.",
author = "Haikun Wang and Jianlin Geng and Xiaomin Wen and Enguang Bi and Kossenkov, {Andrew V.} and Wolf, {Amaya I.} and Jeroen Tas and Choi, {Youn Soo} and Hiroshi Takata and Day, {Timothy J.} and Chang, {Li Yuan} and Sprout, {Stephanie L.} and Becker, {Emily K.} and Jessica Willen and Lifeng Tian and Xinxin Wang and Changchun Xiao and Ping Jiang and Shane Crotty and Victora, {Gabriel D.} and Showe, {Louise C.} and Tucker, {Haley O.} and Jan Erikson and Hui Hu",
note = "Funding Information: We thank K. Rajewsky (Max Delbruck Center for Molecular Medicine) for the Rosa26 targeting vector; E.J. Wherry (University of Pennsylvania) for the SMARTA mice; M.E. Pipkin (The Scripps Research Institute) for the plasmid MigR1-Bcl-6-GFP; N.A. Speck (University of Pennsylvania) for the plasmid MigR1-Cre-GFP; W. Pear (University of Pennsylvania) for the plasmid MSCV-IRES-hNGFR; K. Mozdzanowska and J. Hayden for technical help with histology; J.S. Faust, D.E. Ambrose and S. Weiss for technical help with flow cytometry; M.S. Wright, M. Houston-Leslie and D. DiFrancesco for help at the Animal Facility of the Wistar Institute; and P. Wickramasinghe for help with microarray data and accession codes. Supported by the US National Institutes of Health (AI095439 and AI103162 to H.H.; CA132098 and 1S10RR024693 to L.C.S.; CA31534 to H.O.T.; AI083022 to J.E.; 5DP5OD012146 to G.D.V.; and AI063107 to S.C.), the Alliance for Cell Gene Therapy Foundation (H.H.), the Wawa Foundation (H.H.), the Martha W. Rogers Trust (H.H.), and the Wistar Cancer Center (P30 CA10815).",
year = "2014",
month = jul,
doi = "10.1038/ni.2890",
language = "English (US)",
volume = "15",
pages = "667--675",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "7",
}