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

Hu, Xuqiao1,2,3; Li, Fei3; Zeng, Jieying1; Zhou, Zhenru1; Wang, Zhaoyang1; Chen, Jing1; Cao, Dongyan4; Hong, Yifan5; Huang, Laixin3; Chen, Yongsheng1; Xu, Jinfeng1; Dong, Fajin1; Yu, Rongmin2,6,7; Zheng, Hairong3

2022-12-19

10.34133/research.0013

RESEARCH   Impact Factor & Quartile

2096-5168

2639-5274

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.

SCI

English

First ; Corresponding

Guangdong Basic and Applied Basic Research Foundation[2021A1515110672] ; Shenzhen Science and Technology Program["GJHZ20200731095401004","GJHZ20210705141404012"] ; China Postdoctoral Science Foundation[2021M691262] ; National Natural Science Foundation of China["12074402","82204681"] ; Shenzhen Basic Research Program[JCYJ20200109114825064]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000903432900001

AMER ASSOC ADVANCEMENT SCIENCE

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Ultrasound,Affiliated Hosp 1,Clin Med Coll 2, Shenzhen 518020, Peoples R China
2.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou 510632, Peoples R China
3.Chinese Acad Sci, Inst Biomed & Hlth Engn, Shenzhen Inst Adv Technol, Paul C. Lauterbur Res Ctr Biomed Imaging, 1068 Xueyuan Ave, Shenzhen 518055, Peoples R China
4.Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, Sch Med, Shanghai 200032, Peoples R China
5.Shenzhen Bay Lab, Inst Mol Physiol, Inst Canc Res, Shenzhen 518132, Peoples R China
6.Jinan Univ, Coll Pharm, Dept Pharmacol, 601 Huangpu Ave West, Guangzhou 510632, Peoples R China
7.Jinan Univ, Biotechnol Inst Chinese Mat Med, 601 Huangpu Ave West, Guangzhou 510632, Peoples R China

Hu, Xuqiao,Li, Fei,Zeng, Jieying,et al. Noninvasive Low-Frequency Pulsed Focused Ultrasound Therapy for Rheumatoid Arthritis in Mice[J]. RESEARCH,2022,2022.

Hu, Xuqiao.,Li, Fei.,Zeng, Jieying.,Zhou, Zhenru.,Wang, Zhaoyang.,...&Zheng, Hairong.(2022).Noninvasive Low-Frequency Pulsed Focused Ultrasound Therapy for Rheumatoid Arthritis in Mice.RESEARCH,2022.

Hu, Xuqiao,et al."Noninvasive Low-Frequency Pulsed Focused Ultrasound Therapy for Rheumatoid Arthritis in Mice".RESEARCH 2022(2022).