Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis.

Author: Zachs DP1, Offutt SJ2, Graham RS3, Kim Y2, Mueller J2, Auger JL3, Schuldt NJ3, Kaiser CRW4, Heiller AP4, Dutta R3, Guo H4, Alford JK2, Binstadt BA3, Lim HH5,6,7
Author Information:
1Department of Biomedical Engineering, University of Minnesota, Minneapolis, 55455, MN, USA. zachs001@umn.edu.
2Restorative Therapies Group, Medtronic plc, Minneapolis, 55432, MN, USA.
3Center for Immunology and Department of Pediatrics, University of Minnesota, Minneapolis, 55455, MN, USA.
4Department of Biomedical Engineering, University of Minnesota, Minneapolis, 55455, MN, USA.
5Department of Biomedical Engineering, University of Minnesota, Minneapolis, 55455, MN, USA. hlim@umn.edu.
6Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, 55455, MN, USA. hlim@umn.edu.
7Institute for Translational Neuroscience, University of Minnesota, Minneapolis, 55455, MN, USA. hlim@umn.edu.
Conference/Journal: Nat Commun.
Date published: 2019 Mar 12
Other: Volume ID: 10 , Issue ID: 1 , Pages: 951 , Special Notes: doi: 10.1038/s41467-019-08721-0. , Word Count: 143


Targeted noninvasive control of the nervous system and end-organs may enable safer and more effective treatment of multiple diseases compared to invasive devices or systemic medications. One target is the cholinergic anti-inflammatory pathway that consists of the vagus nerve to spleen circuit, which has been stimulated with implantable devices to improve autoimmune conditions such as rheumatoid arthritis. Here we report that daily noninvasive ultrasound (US) stimulation targeting the spleen significantly reduces disease severity in a mouse model of inflammatory arthritis. Improvements are observed only with specific parameters, in which US can provide both protective and therapeutic effects. Single cell RNA sequencing of splenocytes and experiments in genetically-immunodeficient mice reveal the importance of both T and B cell populations in the anti-inflammatory pathway. These findings demonstrate the potential for US stimulation of the spleen to treat inflammatory diseases.

PMID: 30862842 DOI: 10.1038/s41467-019-08721-0

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