MicroRNA 26a prolongs skin allograft survival and promotes regulatory T cell expansion in mice.

MicroRNA 26a (Mir-26a) has been reported to play functions in cellular differentiation, cell growth, cell apoptosis, and metastasis. However, the role of Mir-26a in transplant rejection has never been investigated. Full-thickness skin grafts 1-2 cm in diameter were obtained from the tail-skin CBA/J donor mice and transplanted onto the back of wild-type C57Bl/6 recipient mice. Vectors encoding pre-Mir-26a (LV-26a) and an empty lentiviral vector (LV-Con) delivered approximately 2 × 10(7) transforming units of recombinant lentivirus were injected to mice once through the tail vein. Mir-26a overexpression results in prolonged skin allograft survival (MST = 9.5 days in LV-Con mice; MST = 22 days in LV-26a mice. P < 0.01) and promoted regulatory T cells (Tregs) expansion. The prolonged skin allograft survival induced by LV-26a was abrogated by depletion of Tregs with anti-CD25 antibodies. Mir-26a significantly promoted IL-10 expression and suppressed the expression of IL-6, IL-17, and IFN-γ. Furthermore, IL-6 overexpression led to complete suppression of the Mir-26a-induced upregulation of Foxp3. The prolonged allograft survival induced by LV-Mir-26a was also completely abrogated by IL-6 overexpression. In conclusion, Mir-26a prolongs skin allograft survival and promotes Tregs expansion in part through inhibition of IL-6 expression.