The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells

Haikun Wang, Jianlin Geng, Xiaomin Wen, Enguang Bi, Andrew V. Kossenkov, Amaya I. Wolf, Jeroen Tas, Youn Soo Choi, Hiroshi Takata, Timothy J. Day, Li Yuan Chang, Stephanie L. Sprout, Emily K. Becker, Jessica Willen, Lifeng Tian, Xinxin Wang, Changchun Xiao, Ping Jiang, Shane Crotty, Gabriel D. VictoraLouise C. Showe, Haley O. Tucker, Jan Erikson, Hui Hu

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)667-675
Number of pages9
JournalNature Immunology
Volume15
Issue number7
DOIs
StatePublished - Jul 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells'. Together they form a unique fingerprint.

Cite this