Noninvasive Low-Frequency Pulsed Focused Ultrasound Therapy for Rheumatoid Arthritis in Mice  

作　　者：Xuqiao Hu Fei Li Jieying Zeng Zhenru Zhou Zhaoyang Wang Jing Chen Dongyan Cao Yifan Hong Laixin Huang Yongsheng Chen Jinfeng Xu Fajn Dong Rongmin Yu Harong Zhen 

机构地区：[1]Department of Ultrasound,First Affiliated Hospital of Southern University of Science and Technology,Second Clinical Medical College of Jinan University(Shenzhen People's Hospital),Shenzhen 518020,China [2]integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou 510632,China [3]Paul C.Lauterbur Research Center for Biomedical Imaging,Institute of Biomedical and Health Engineering,Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,1068 Xueyuan Avenue,Shenzhen University Town,Shenzhen 518055,China [4]Shanghai Cancer Institute,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200032,China [5]institute of Molecular Physiology,Institute of Cancer Research,Shenzhen Bay Laboratory,Shenzhen 518132,P.R.China [6]Department of Pharmacology,College of Pharmacy,Jinan University,601 Huangpu Avenue West,Guangzhou 510632,China [7]Biotechnological Institute of Chinese Materia Medica,Jinan University,601 Huangpu Avenue West,Guangzhou 510632,China

出　　处：《Research》2023年第3期205-219,共15页研究（英文）

基　　金：the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110672);Shenzhen Science and Technology Program(No.GJHZ20200731095401004 and No.GJHZ20210705141404012);the China Postdoctoral Science Foundation(No.2021M691262);the National Natural Science Foundation of China(No.12074402 and No.82204681);the Shenzhen Basic Research Program(No.JCYJ20200109114825064).

摘　　要：Rheumatoid arthritis(RA)is a common autoimmune disease characterized by chronic and progressive inflammation of the synovium.Focused ultrasound therapy is an increasingly attractive alternative for treating RA owing to its noninvasiveness;however,it remains unclear which immune subsets respond to ultrasound stimulation.In this study,we showed that spleen-targeted low-frequency pulsed focused ultrasound(LFPFU)effectively improved the severity of arthritis in an arthritis mouse model established in DBA/1J mice.Additionally,we performed in-depth immune profiling of spleen samples from RA mice,RA mice that underwent ultrasound therapy,and healthy controls using mass cytometry along with extensive antibody panels and identified the immune composition of 14 cell populations,including CD4^(+)/CD8^(+)T cells,B cells,natural killer cells,and dendritic cells.Moreover,multidimensional analysis according to cell-surface markers and phenotypes helped in identifying 4 and 5 cell subpopulations among T and myeloid cells,respectively,with 6 T cell subsets and 3 myeloid cell subsets responsive to ultrasound therapy among the 3 groups.Of these cell subsets,CD8^(+)T cell subsets showed a unique response to ultrasound stimulation in RA mice.Specifically,CD8^(+)T cells show a noticeable correlation with the degree of arthritis progression and could serve as an indicator for spleen-focused ultrasound-based therapy.Furthermore,single-cell RNA sequencing of spleen cells revealed the importance of T,B,and myeloid cell populations in the anti-inflammatory pathway.These results elucidated the unique cell subsets and transcriptome of splenic cells responsive to LFPFU and demonstrated the potential of spleen-focused ultrasound stimulation in the treatment of inflammatory diseases.

关 键 词：SPLEEN STIMULATION Focus 

分 类 号：R73[医药卫生—肿瘤]