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

Li Wen Lai, Kim Chong Yong, Yeong Hau H. Lien

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)983-992
Number of pages10
JournalKidney International
Volume81
Issue number10
DOIs
StatePublished - May 2 2012

Keywords

  • Acute kidney injury
  • Chemokine
  • Lymphocytes
  • Renal ischemia-reperfusion
  • TNF

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Pharmacologic recruitment of regulatory T cells as a therapy for ischemic acute kidney injury'. Together they form a unique fingerprint.

Cite this