miR-204-containing exosomes ameliorate GVHD-associated dry eye disease.
miR-204-containing exosomes ameliorate GVHD-associated dry eye disease.
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含有 miR-204 的外泌体可改善 GVHD 相关的干眼病。
DOI：
10.1126/sciadv.abj9617
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发表时间：
2022-01-14
期刊：
影响因子：
13.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Zhou T;He C;Lai P;Yang Z;Liu Y;Xu H;Lin X;Ni B;Ju R;Yi W;Liang L;Pei D;Egwuagu CE;Liu X
MSC-exo滴眼液通过miR-204将M1巨噬细胞转移到M2来缓解GVHD相关的干眼病移植物抗宿主病（GVHD）相关的干眼病的特征在于眼表中广泛的炎性破坏，并引起难以忍受的疼痛和视力损害。目前的治疗提供有限的好处。在这里，我们报告了来自间充质基质细胞（MSC-exo）的外泌体作为滴眼剂给药，通过抑制炎症和改善小鼠和人类的上皮恢复来显著减轻GVHD相关的干眼病。在一项前瞻性临床试验中，28只患有难治性GVHD-干眼病的眼睛在MSC-exo治疗后表现出显著缓解，表现出荧光素评分降低、泪膜破裂时间延长、泪液分泌增加和OSDI评分降低。从机制上讲，MSC-exo通过miR-204介导的IL-6/IL-6 R/Stat 3通路靶向将促炎性M1巨噬细胞重编程为免疫抑制性M2。miR-204的阻断消除了MSC-exo的作用，而用miR-204使L929-exo过载显著减弱了干眼。因此，这项研究表明，MSC-exo在治疗GVHD相关的干眼病中是有效的，并强调了miR-204作为一种潜在的治疗剂。
MSC-exo eye drops alleviate GVHD-associated dry eye disease by shifting M1 macrophages to M2 via miR-204. Graft-versus-host disease (GVHD)–associated dry eye disease is characterized by extensive inflammatory destruction in the ocular surface and causes unbearable pain and visual impairment. Current treatments provide limited benefits. Here, we report that exosomes from mesenchymal stromal cells (MSC-exo) administered as eye drops notably alleviate GVHD-associated dry eye disease by suppressing inflammation and improving epithelial recovery in mice and humans. In a prospective clinical trial, 28 eyes with refractory GVHD–dry eye disease exhibited substantial relief after MSC-exo treatment, showing reduced fluorescein scores, longer tear-film breakup time, increased tear secretion, and lower OSDI scores. Mechanistically, MSC-exo reprogramed proinflammatory M1 macrophages toward the immunosuppressive M2 via miR-204–mediated targeting of the IL-6/IL-6R/Stat3 pathway. Blockade of miR-204 abolished the effects of MSC-exo, while overloading L929-exo with miR-204 markedly attenuated dry eye. Thus, this study suggests that MSC-exo are efficacious in treating GVHD-associated dry eye disease and highlights miR-204 as a potential therapeutic agent.
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影响因子：
16
作者：
Iwai K;Minamisawa T;Suga K;Yajima Y;Shiba K
通讯作者：
Shiba K
影响因子：
6.4
作者：
Latta, L.;Ludwig, N.;Kaesmann-Kellner, B.
通讯作者：
Kaesmann-Kellner, B.
影响因子：
13.7
作者：
Abud TB;Amparo F;Saboo US;Di Zazzo A;Dohlman TH;Ciolino JB;Hamrah P;Dana R
通讯作者：
Dana R
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
6
作者：
Doeppner TR;Bähr M;Hermann DM;Giebel B
通讯作者：
Giebel B