Pre-B cell leukemia homeobox 1 is associated with lupus susceptibility in mice and humans

Carla M. Cuda, Shiwu Li, Shujuan Liang, Yiming Yin, Hari Hara S.K. Potula, Zhiwei Xu, Mayami Sengupta, Yifang Chen, Edward Butfiloski, Henry Baker, Lung Ji Chang, Igor Dozmorov, Eric S. Sobel, Laurence Morel

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Sle1a.1 is part of the Sle1 susceptibility locus, which has the strongest association with lupus nephritis in the NZM2410 mouse model. In this study, we show that Sle1a.1 results in the production of activated and autoreactive CD4 + T cells. Additionally, Sle1a.1 expression reduces the peripheral regulatory T cell pool, as well as induces a defective response of CD4 + T cells to the retinoic acid expansion of TGF-β-induced regulatory T cells. At the molecular level, Sle1a.1 corresponds to an increased expression of a novel splice isoform of Pbx1, Pbx1-d. Pbx1-d overexpression is sufficient to induce an activated/inflammatory phenotype in Jurkat T cells and to decrease their apoptotic response to retinoic acid. PBX1-d is expressed more frequently in the CD4 + T cells from lupus patients than from healthy controls, and its presence correlates with an increased central memory T cell population. These findings indicate that Pbx1 is a novel lupus susceptibility gene that regulates T cell activation and tolerance.

Original languageEnglish (US)
Pages (from-to)604-614
Number of pages11
JournalJournal of Immunology
Volume188
Issue number2
DOIs
StatePublished - Jan 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Cuda, C. M., Li, S., Liang, S., Yin, Y., Potula, H. H. S. K., Xu, Z., Sengupta, M., Chen, Y., Butfiloski, E., Baker, H., Chang, L. J., Dozmorov, I., Sobel, E. S., & Morel, L. (2012). Pre-B cell leukemia homeobox 1 is associated with lupus susceptibility in mice and humans. Journal of Immunology, 188(2), 604-614. https://doi.org/10.4049/jimmunol.1002362