title: MicroRNA 26a prolongs skin allograft survival and promotes regulatory T cell expansion in mice.
abstract: 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.
authors: Department of Plastic Surgery, Henan Province People's Hospital, Zhengzhou, China.|Department of Burn, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors: Feng
authors: F
authors: Xie
authors: Department of Burn, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors: Jiake
authors: J
authors: Chai
authors: Department of Plastic Surgery, Henan Province People's Hospital, Zhengzhou, China.
authors: Zhengwen
authors: Z
authors: Zhang
authors: Department of Burn, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors: Quan
authors: Q
authors: Hu
authors: Department of Plastic Surgery, Henan Province People's Hospital, Zhengzhou, China.
authors: Tengxiao
authors: T
authors: Ma
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D064591:Allografts; D000818:Animals; D002455:Cell Division; D015536:Down-Regulation; D005822:Genetic Vectors / Q000235:genetics; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000172:deficiency; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; C556062:IL10 protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; C039919:RNA, recombinant; D016753:Interleukin-10; D012313:RNA; D007371:Interferon-gamma
keywords: IL-10; IL-6; Mir-26a; Tregs; skin allograft rejection