RGD Reference Report - Elevated CXCL12 expression in the bone marrow of NOD mice is associated with altered T cell and stem cell trafficking and diabetes development. - Rat Genome Database

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Elevated CXCL12 expression in the bone marrow of NOD mice is associated with altered T cell and stem cell trafficking and diabetes development.

Authors: Leng, Q  Nie, Y  Zou, Y  Chen, J 
Citation: Leng Q, etal., BMC Immunol. 2008 Sep 15;9:51.
RGD ID: 2301942
Pubmed: PMID:18793419   (View Abstract at PubMed)
PMCID: PMC2556327   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2172-9-51   (Journal Full-text)

BACKGROUND: Type I diabetes (TID) is an autoimmune disease resulting from destruction of the insulin-producing beta-cells by autoreactive T cells. Studies have shown that polymorphisms of chemokine CXCL12 gene are linked to TID in humans. In non-obese diabetic (NOD) mice, which are predisposed to develop the disease, reduction of CXCL12 level leads to significant delays in the onset of diabetes. Despite these initial observations, however, how CXCL12 affects development of TID has not been fully investigated. RESULTS: We found that the level of CXCL12 transcript is significantly elevated in the bone marrow of NOD mice as compared to Balb/c and C57BL/6 mice. Correspondingly, naive T cells, regulatory T cells and hematopoietic stem cells (HSC) accumulate in the bone marrow of NOD mice. Treatment of NOD mice with AMD3100, an antagonist for CXCL12's receptor CXCR4, mobilizes T cells and HSC from the bone marrow to the periphery, concomitantly inhibits insulitis and delays the onset of diabetes. CONCLUSION: These results suggest that the elevated CXCL12 expression promotes TID in NOD mice by altering T cell and hematopoietic stem cell trafficking. The findings highlight the potential usefulness of AMD3100 to treat or prevent TID in humans.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 1 diabetes mellitus onsetISOCxcl12 (Mus musculus)2301942; 2301942mRNA:increased expression:bone marrowRGD 
type 1 diabetes mellitus onsetIMP 2301942mRNA:increased expression:bone marrowRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcl12  (C-X-C motif chemokine ligand 12)

Genes (Mus musculus)
Cxcl12  (C-X-C motif chemokine ligand 12)

Genes (Homo sapiens)
CXCL12  (C-X-C motif chemokine ligand 12)


Additional Information