Photophosphatidylserine Guides Natural Killer Cell Photoimmunotherapy via Tim-3

被引:19
|
作者
Yang, Xingye [1 ]
Li, Mengzhen [2 ,3 ]
Qin, Xiaojun [1 ]
Tan, Siyu [2 ,3 ]
Du, Lupei [1 ]
Ma, Chunhong [2 ,3 ,4 ]
Li, Minyong [1 ,5 ,6 ]
机构
[1] Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Dept Med Chem,Key Lab Chem Biol MOE, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Cheeloo Coll Med, Sch Basic Med Sci, Key Lab Expt Teratol,Minist Educ, Jinan 250012, Shandong, Peoples R China
[3] Shandong Univ, Cheeloo Coll Med, Sch Basic Med Sci, Dept Immunol, Jinan 250012, Shandong, Peoples R China
[4] Shandong Univ, Cheeloo Coll Med, Sch Basic Med Sci, Key Lab Infect & Immun Shandong Prov, Jinan 250012, Shandong, Peoples R China
[5] Shandong Univ, Cheeloo Coll Med, Adv Med Res Inst, Jinan 250012, Shandong, Peoples R China
[6] Shandong Univ, Helmholtz Int Lab, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
MOLONEY LEUKEMIA-CELLS; IMMUNE-RESPONSES; CYTOTOXIC-CELLS; OPTICAL CONTROL; PHOSPHATIDYLSERINE; MOUSE; STIMULATION; SPECIFICITY; EXHAUSTION; AZOBENZENE;
D O I
10.1021/jacs.1c11498
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Natural killer (NK) cells, in addition to their cytotoxicity function, harbor prominent cytokine production capabilities and contribute to regulating autoimmune responses. T-cell immunoglobulin and mucin domain containing protein-3 (Tim-3) is one of the inhibitory receptors on NK cells and a promising immune checkpoint target. We recently found that phosphatidylserine (PS) binding to Tim-3 can suppress NK cell activation. Therefore, based on the therapeutic potential of Tim-3 in NK-cell-mediated diseases, we developed a photoswitchable ligand of Tim-3, termed photophosphatidylserine (phoPS), that mimics the effects of PS. Upon 365 or 455 nm light irradiation, the isomer of phoPS cyclically conversed the cis/trans configuration, resulting in an active/inactive Tim-3 ligand, thus modulating the function of NK cells in vitro and in vivo. We also demonstrated that reversible phoPS enabled optical control of acute hepatitis. Together, phoPS may be an appealing tool for autoimmune diseases and cytokine storms in the future.
引用
收藏
页码:3863 / 3874
页数:12
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