Unknown,Transcriptomics,Genomics,Proteomics

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Pre-B cell leukemia homeobox protein Pbx1 is associated with lupus susceptibility in mice and humans


ABSTRACT: Sle1a.1 is part of the Sle1a lupus susceptibility locus which results in the production of activated and autoreactive CD4+ T cells as well as a reduction in the peripheral regulatory T cell (Treg) pool. Sle1a.1 CD4+ T cells showed a defective response to retinoic acid (RA) expansion of TGFβ-induced Tregs. At the molecular level, Sle1a.1 corresponds to an increased expression of a novel splice isoform of Pbx1, Pbx1-d. Pbx1-d over-expression is sufficient to induce an activated/inflammatory phenotype in Jurkat T cells, and to decrease their apoptotic response to RA. PBX1-d is expressed more frequently in lupus patients than in healthy controls, and its presence correlates with an increased memory T cell population. These findings indicate that Pbx1 is a novel lupus susceptibility gene that regulates T cell activation and tolerance. Total RNA from CD4+ T cells from C57BL/6 (B6) and B6.Sle1a.1 (Sle) mice was isolated, with 4 biological replicates each. Gene expression data from C57BL/6 mice were compared with data from B6.Sle2c1 mice.

ORGANISM(S): Mus musculus

SUBMITTER: Zhiwei Xu 

PROVIDER: E-GEOD-22313 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Cuda Carla M CM   Li Shiwu S   Liang Shujuan S   Yin Yiming Y   Potula Hari Hara S K HH   Xu Zhiwei Z   Sengupta Mayami M   Chen Yifang Y   Butfiloski Edward E   Baker Henry H   Chang Lung-Ji LJ   Dozmorov Igor I   Sobel Eric S ES   Morel Laurence L  

Journal of immunology (Baltimore, Md. : 1950) 20111216 2


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 i  ...[more]

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