Analysis of the bioactive molecules that enhance the induction and suppressive properties of human regulatory T cells and application to therapy

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We screened 14 kinds of the molecules that enhanced the induction and suppressive function of human regulatory T cells(Treg) from lipid and nuclear receptor ligand libraries. Of these, PPAR agonists increased suppressive function and expression of Foxp3 in induced Tregs(iTregs). PPAR agonist-treated iTregs increased demethylation level of the Foxp3 promoter region and CNS3. Moreover, TSA and ATRA enhanced iTregs generation synergistically with PPAR agonists. On the other hand, lysophosphatidylcholine(LPC) enhances Foxp3 expression and the suppressive function of nTregs through TGF-beta1 produced by nTregs themselves. These agents increased Treg differentiation and induction and may be benefical for the treatment of human autoimmune diseases.