RGD Reference Report - Pharmacologic recruitment of regulatory T cells as a therapy for ischemic acute kidney injury. - Rat Genome Database

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Pharmacologic recruitment of regulatory T cells as a therapy for ischemic acute kidney injury.

Authors: Lai, LW  Yong, KC  Lien, YH 
Citation: Lai LW, etal., Kidney Int. 2012 May;81(10):983-92. doi: 10.1038/ki.2011.412. Epub 2011 Dec 21.
RGD ID: 7204675
Pubmed: PMID:22189844   (View Abstract at PubMed)
PMCID: PMC3340526   (View Article at PubMed Central)
DOI: DOI:10.1038/ki.2011.412   (Journal Full-text)

Regulatory T cells (Tregs) are key components of the peripheral tolerance system and have become an immunotherapeutic agent for treating inflammatory processes. This therapeutic option, however, is hampered by problems arising from isolating and expanding desirable Tregs. Here we used an alternative approach with a pharmacologic agent to stimulate Tregs to achieve immunosuppressive effects. Pretreatment of mice with the naturally occurring sphingosine N,N-dimethylsphingosine (DMS) was found to increase both tissue-infiltrating T effectors (Teffs, CD4(+)Foxp3(-)) and Tregs (CD4(+)Foxp3(+)) in the early phase of bilateral renal ischemia/reperfusion injury. DMS itself had no effects on renal function or histopathology, but rapidly and transiently increased both Teffs and Tregs and increased the expression of chemokines CXCL9, CCL5, and CXCL10 in non-ischemic kidneys (sham operation). This renoprotection was abolished by administration of the Treg suppressing agents, anti-CTLA-4 or anti-CD25 monoclonal antibodies, suggesting that Tregs play a key role in DMS-induced renoprotection. Thus, Tregs recruited to the kidney by DMS ameliorate acute kidney injury and provide a new approach to control inflammatory diseases.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Kidney Reperfusion Injury  ISOCtla4 (Mus musculus)7204675; 7204675 RGD 
Kidney Reperfusion Injury  IMP 7204675 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ctla4  (cytotoxic T-lymphocyte-associated protein 4)

Genes (Mus musculus)
Ctla4  (cytotoxic T-lymphocyte-associated protein 4)

Genes (Homo sapiens)
CTLA4  (cytotoxic T-lymphocyte associated protein 4)


Additional Information