TY - JOUR
T1 - Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response
AU - Tanno, Hiromasa
AU - Kawakami, Kazuyoshi
AU - Kanno, Emi
AU - Suzuki, Aiko
AU - Takagi, Naoyuki
AU - Yamamoto, Hideki
AU - Ishii, Keiko
AU - Imai, Yoshimichi
AU - Maruyama, Ryoko
AU - Tachi, Masahiro
N1 - Funding Information:
Source of Funding: This work was supported in part by a Grant-in-Aid for Scientific Research (B) (16H05492), Grant-in-Aid for Research Activity start-up (15H06052), and Grant-in-Aid for Young Scientists (B) (17K17393) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Publisher Copyright:
© 2017 by the Wound Healing Society
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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 (Jα18KO 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 Jα18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in Jα18KO 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 Jα18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils.
AB - 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 (Jα18KO 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 Jα18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in Jα18KO 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 Jα18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils.
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U2 - 10.1111/wrr.12588
DO - 10.1111/wrr.12588
M3 - Article
C2 - 28940971
AN - SCOPUS:85040200688
VL - 25
SP - 805
EP - 815
JO - Wound Repair and Regeneration
JF - Wound Repair and Regeneration
SN - 1067-1927
IS - 5
ER -