GeneSet Information

Tier II GS136700 • systemic lupus erythmatosus susceptibility 2 (Sle2, Published QTL Chr 4)

DESCRIPTION:

QTL associated with systemic lupus erythmatosus susceptibility 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (82636691)

LABEL:

QTL-Sle2-Mouse-Chr 4

SCORE TYPE:

Binary

DATE ADDED:

2012-04-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Xu Z, Vallurupalli A, Fuhrman C, Ostrov D, Morel L

TITLE:

A New Zealand Black-derived locus suppresses chronic graft-versus-host disease and autoantibody production through nonlymphoid bone marrow-derived cells.

JOURNAL:

Journal of immunology (Baltimore, Md. : 1950) Apr 2011, Vol 186, pp. 4130-9

ABSTRACT:

The development of lupus pathogenesis results from the integration of susceptibility and resistance genes. We have used a chronic graft-versus-host disease (cGVHD) model to characterize a suppressive locus at the telomeric end of the NZM2410-derived Sle2 susceptibility locus, which we named Sle2c2. cGVHD is induced normally in Sle2c2-expressing mice, but it is not sustained. The analysis of mixed bone marrow chimeras revealed that cGVHD resistance was eliminated by non-B non-T hematopoietic cells expressing the B6 allele, suggesting that resistance is mediated by this same cell type. Furthermore, Sle2c2 expression was associated with an increased number and activation of the CD11b(+) GR-1(+) subset of granulocytes before and in the early stage of cGVHD induction. We have mapped the Sle2c2 critical interval to a 6-Mb region that contains the Cfs3r gene, which encodes for the G-CSFR, and its NZM2410 allele carries a nonsynonymous mutation. The G-CSFR-G-CSF pathway has been previously implicated in the regulation of GVHD, and our functional data on Sle2c2 suppression suggest a novel regulation of T cell-induced systemic autoimmunity through myeloid-derived suppressor cells. The validation of Csf3r as the causative gene for Sle2c2 and the further characterization of the Sle2c2 MDSCs promise to unveil new mechanisms by which lupus pathogenesis is regulated. PUBMED: 21335485
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Annotation Information

No sequence read archive data associated with this GeneSet.


Social Control, Formal (D012926)
Granulocytes (D006098)
Alleles (D000483)
Bone Marrow (D001853)
New Zealand (D009520)
Graft vs Host Disease (D006086)
Chimera (D002678)
Bone and Bones (D001842)
Autoimmunity (D015551)
Mutation (D009154)
bone marrow (MA:0000134)
pathogenesis (GO:0009405)

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