The lupus susceptibility gene Pbx1 regulates the balance between follicular helper t cell and regulatory t cell differentiation

Seung Chul Choi, Tarun E. Hutchinson, Anton A. Titov, Howard R. Seay, Shiwu Li, Todd M. Brusko, Byron P. Croker, Shahram Salek-Ardakani, Laurence Morel

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Pbx1 controls chromatin accessibility to a large number of genes and is entirely conserved between mice and humans. The Pbx1-d dominant-negative isoform is more frequent in CD4+ T cells from lupus patients than from healthy controls. Pbx1-d is associated with the production of autoreactive T cells in mice carrying the Sle1a1 lupus-susceptibility locus. Transgenic (Tg) expression of Pbx1-d in CD4+ T cells reproduced the phenotypes of Sle1a1 mice, with increased inflammatory functions of CD4+ T cells and impaired Foxp3+ regulatory T cell (Treg) homeostasis. Pbx1-d-Tg expression also expanded the number of follicular helper T cells (TFHs) in a cell-intrinsic and Ag-specific manner, which was enhanced in recall responses and resulted in Th1-biased Abs. Moreover, Pbx1-d-Tg CD4+ T cells upregulated the expression of miR-10a, miR-21, and miR-155, which were implicated in Treg and follicular helper T cell homeostasis. Our results suggest that Pbx1-d impacts lupus development by regulating effector T cell differentiation and promoting TFHs at the expense of Tregs. In addition, our results identify Pbx1 as a novel regulator of CD4+ T cell effector function.

Original languageEnglish (US)
Pages (from-to)458-469
Number of pages12
JournalJournal of Immunology
Volume197
Issue number2
DOIs
StatePublished - Jul 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'The lupus susceptibility gene Pbx1 regulates the balance between follicular helper t cell and regulatory t cell differentiation'. Together they form a unique fingerprint.

Cite this