IL-36 receptor antagonist deficiency resulted in delayed wound healing due to excessive recruitment of immune cells
IL-36 receptor antagonist deficiency resulted in delayed wound healing due to excessive recruitment of immune cells
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IL-36 受体拮抗剂缺乏导致免疫细胞过度募集导致伤口愈合延迟
DOI：
10.1038/s41598-020-71256-8
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发表时间：
2020
影响因子：
4.6
通讯作者：
K. Sugiura
中科院分区：
文献类型：
--
作者：
Kenta Saito;Y. Iwata;Hidehiko Fukushima;Soichiro Watanabe;Yoshihito Tanaka;Y. Hasegawa;M. Akiyama;K. Sugiura
编码白介素-36受体拮抗剂（IL-36Ra）的IL36RN的功能丧失纯合或复合杂合突变与各种皮肤疾病的发病机制有关。先前的研究结果表明，IL-36γ促进小鼠伤口愈合；然而，IL-36Ra在伤口愈合中的致病作用尚不清楚。我们通过研究IL-36Ra缺失时炎症细胞的募集和细胞因子的产生，阐明了IL-36Ra在组织修复中的作用。IL-36Ra是IL-36的调节因子。在Il36rn−/−小鼠背部制作全层切除伤口，通过监测宏观伤口大小、浸润细胞数量和炎症细胞因子的基因表达来评估愈合情况。Il36rn−/−小鼠损伤后3天肉眼可见的伤口愈合、再上皮化和肉芽组织形成延迟。这种延迟与中性粒细胞和巨噬细胞浸润增加以及细胞因子表达增加有关，如IL-36γ、C-X-C基序趋化因子配体1 （CXCL1）和转化生长因子(TGF)-β。重要的是，给予toll样受体4 （TLR4）抑制剂TAK-242，可使Il36rn−/−小鼠的伤口愈合正常化，消除组织修复的初始延迟。这些结果表明，靶向TLR4介导的免疫细胞浸润和细胞因子的产生可能有助于调节il - 36ra缺乏性皮肤疾病的伤口愈合。
Loss-of-function homozygous or compound heterozygous mutations in IL36RN, which encodes interleukin-36 receptor antagonist (IL-36Ra), have been implicated in the pathogenesis of various skin disorders. Previous findings showed that IL-36γ promoted wound healing in mice; however, the pathogenic role of IL-36Ra in wound healing remains unclear. We elucidated the role of IL-36Ra, a regulator of IL-36 in tissue repair by investigating the recruitment of inflammatory cells and cytokine production in the absence of IL-36Ra. Full-thickness excisional wounds were made on the back of Il36rn−/− mice and healing was assessed by monitoring macroscopic wound sizes, numbers of infiltrated cells, and gene expression of inflammatory cytokines. Macroscopic wound healing, re-epithelialization, and granulation tissue formation were delayed by 3 days post-injury in Il36rn−/− mice. This delay was associated with increased infiltrations of neutrophils and macrophages, and increased expression of cytokines, such as IL-36γ, C-X-C motif chemokine ligand 1 (CXCL1), and transforming growth factor (TGF)-β. Importantly, administration of TAK-242, a toll-like receptor 4 (TLR4) inhibitor, caused normalization of wound healing in Il36rn−/− mice, abrogating the initial delay in tissue repair. These results showed that targeting TLR4- mediated infiltrations of immune cells and cytokine production could be beneficial in regulating wound healing in IL-36Ra-deficient skin disorders.
影响因子：
5.9
作者：
Dong, Di;Tukker, Arnold;Van der Voet, Ester
通讯作者：
Van der Voet, Ester
DOI：
10.1165/rcmb.2010-0075oc
发表时间：
2011-07-01
影响因子：
6.4
作者：
Chustz, Regina T.;Nagarkar, Deepti R.;Kato, Atsushi
通讯作者：
Kato, Atsushi