Nuclear receptors and autoimmune disease: The potential of PPAR agonists to treat multiple sclerosis

Michael K. Racke, Anne R. Gocke, Mark Muir, Asim Diab, Paul D. Drew, Amy E. Lovett-Racke

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated, autoimmune disorder characterized by central nervous system inflammation and demyelination, features reminiscent of the human disease, multiple sclerosis (MS). Prior work in the EAE model has suggested that encephalitogenic T cells are of the T helper (Th)-1 phenotype. Our group has performed several studies in the EAE model that suggest that a strategy for treating autoimmune disorders is to convert the pathogenic cells from the Th1 to Th2 phenotype. Peroxisome proliferator-activated receptors (PPARs) are members of a nuclear hormone receptor superfamily that include receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response. Recently, we examined the role of PPARγ in EAE and observed that administration of the PPARγ agonist 15-deoxy-Δ12,14 prostaglandin J2 exerted a significant therapeutic effect predominantly by inhibiting the activation and expansion of encephalitogenic T cells. One potential advantage in studying PPARα agonists is that they have been very well tolerated when used in humans to treat conditions such as elevated triglycerides. Building on prior work in immune deviation and with PPAR agonists, we have demonstrated that PPARα agonists can alter the cytokine phenotype of myelin-reactive T cells, alter their encephalitogenicity, and be useful in the treatment of EAE. The fact that PPARα agonists have been used as therapeutic agents in humans to treat metabolic conditions for over 25 years with little toxicity makes them attractive candidates for use as adjunctive therapies in MS.

Original languageEnglish (US)
Pages (from-to)700-703
Number of pages4
JournalJournal of Nutrition
Issue number3
StatePublished - Mar 2006
Externally publishedYes


  • Autoimmunity
  • Cytokines
  • Multiple sclerosis
  • Nuclear receptors
  • PPAR

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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