Tanno Hiromasa, Kawakami Kazuyoshi, Ritsu Masae, Kanno Emi, Suzuki Aiko, Kamimatsuno Rina, Takagi Naoyuki, Miyasaka Tomomitsu, Ishii Keiko, Imai Yoshimichi, Maruyama Ryoko, Tachi Masahiro
Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Am J Pathol. 2015 Dec;185(12):3248-57. doi: 10.1016/j.ajpath.2015.08.012.
In the present study, we determined the contribution of invariant natural killer T (iNKT) cells to the skin wound healing process. In iNKT cell-deficient (Jα18KO) mice lacking iNKT cells, wound closure was significantly delayed compared with wild-type mice. Collagen deposition, expression of α-smooth muscle actin and CD31, and wound breaking strength were significantly attenuated in Jα18KO mice. The adoptive transfer of liver mononuclear cells from wild-type but not from Jα18KO or interferon (IFN)-γ gene-disrupted (IFN-γKO) mice resulted in the reversal of this impaired wound healing in Jα18KO mice. IFN-γ expression was induced in the wounded tissues, which was significantly decreased at 6, 12, and 24 hours, but increased on day 3 after wounding in Jα18KO mice. The main source of the late-phase IFN-γ production in Jα18KO mice were neutrophils rather than NK cells and T cells. Administration of α-galactosylceramide, an activator of iNKT cells, resulted in the acceleration of wound healing on day 3 in wild-type mice. This effect was not observed in IFN-γKO mice. These results indicate that iNKT cells play important roles in wound healing. The iNKT cell-induced IFN-γ production may regulate the wound healing process in the early phase.
在本研究中，我们确定了不变自然杀伤T（iNKT）细胞对皮肤伤口愈合过程的作用。在缺乏iNKT细胞的iNKT细胞缺陷（Jα18KO）小鼠中，与野生型小鼠相比，伤口闭合明显延迟。Jα18KO小鼠的胶原蛋白沉积、α平滑肌肌动蛋白和CD31的表达以及伤口抗张强度均显著减弱。将野生型而非Jα18KO或干扰素（IFN）-γ基因敲除（IFN-γKO）小鼠的肝脏单核细胞进行过继转移，可逆转Jα18KO小鼠受损的伤口愈合。在受伤组织中可诱导IFN-γ表达，在Jα18KO小鼠中，该表达在6、12和24小时时显著降低，但在受伤后第3天增加。Jα18KO小鼠晚期IFN-γ产生的主要来源是中性粒细胞而非NK细胞和T细胞。给予iNKT细胞激活剂α-半乳糖神经酰胺可加速野生型小鼠在第3天的伤口愈合。在IFN-γKO小鼠中未观察到这种作用。这些结果表明，iNKT细胞在伤口愈合中起重要作用。iNKT细胞诱导的IFN-γ产生可能在早期阶段调节伤口愈合过程。
