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J Immunol. 2016 Jul 15;197(2):458-69. doi: 10.4049/jimmunol.1502283. Epub 2016 Jun 13.

The Lupus Susceptibility Gene Pbx1 Regulates the Balance between Follicular Helper T Cell and Regulatory T Cell Differentiation.

Author information

1
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610.
2
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610 morel@ufl.edu.

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.

PMID:
27296664
PMCID:
PMC4935607
DOI:
10.4049/jimmunol.1502283
[Indexed for MEDLINE]
Free PMC Article

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