Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response
Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response
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DOI：
10.1111/wrr.12588
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发表时间：
2017-09-01
影响因子：
2.9
通讯作者：
Tachi, Masahiro
中科院分区：
文献类型：
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作者：
Tanno, Hiromasa;Kawakami, Kazuyoshi;Tachi, Masahiro
伤口愈合过程包括炎症、增殖和重塑三个阶段。在慢性伤口中，炎症期延长，中性粒细胞持续浸润。炎症反应是由各种免疫细胞分泌的细胞因子和趋化因子调控的。最近，我们发现在缺乏不变的自然杀伤T （iNKT）细胞的情况下，皮肤伤口愈合延迟，愈合过程受损，iNKT细胞是一种具有强免疫调节活性的先天免疫淋巴细胞。在本研究中，我们研究了iNKT细胞缺乏对伤口愈合过程中中性粒细胞炎症反应的影响。在受伤后第1天和第3天，基因缺乏iNKT细胞的小鼠（J18KO小鼠）伤口组织中的中性粒细胞浸润时间比野生型（WT）对照小鼠长。J18KO小鼠的MIP-2、KC和IL-17A的产生水平明显高于WT小鼠。此外，J18KO小鼠创面组织中性粒细胞凋亡明显少于WT小鼠。抗il - 17a单抗、抗gr -1单抗或中性粒细胞弹性酶抑制剂治疗可逆转J18KO小鼠的伤口愈合受损。这些结果表明，iNKT细胞可能通过阻止中性粒细胞介导的长时间炎症反应来促进伤口愈合过程。
The wound-healing process consists of the inflammation, proliferation, and remodeling phases. In chronic wounds, the inflammation phase is prolonged with persistent neutrophil infiltration. The inflammatory response is critically regulated by cytokines and chemokines that are secreted from various immune cells. Recently, we showed that skin wound healing was delayed and the healing process was impaired under conditions lacking invariant natural killer T (iNKT) cells, an innate immune lymphocyte with potent immuno-regulatory activity. In the present study, we investigated the effect of iNKT cell deficiency on the neutrophilic inflammatory response during the wound healing process. Neutrophil infiltration was prolonged in wound tissue in mice genetically lacking iNKT cells (J18KO mice) than in wild-type (WT) control mice on days 1 and 3 after wounding. MIP-2, KC, and IL-17A were produced at a significantly higher level in J18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in J18KO mice than in WT mice. Treatment with anti-IL-17A mAb, anti-Gr-1 mAb, or neutrophil elastase inhibitor reversed the impaired wound healing in J18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils.