| Title |
Protection of Tregs, Suppression of Th1 and Th17 Cells, and Amelioration of Experimental Allergic Encephalomyelitis by a Physically-Modified Saline
|
|---|---|
| Published in |
PLOS ONE, December 2012
|
| DOI | 10.1371/journal.pone.0051869 |
| Pubmed ID | |
| Authors |
Susanta Mondal, Jeffrey A. Martinson, Supurna Ghosh, Richard Watson, Kalipada Pahan |
| Abstract |
In multiple sclerosis (MS) and other autoimmune diseases, the autoreactive T cells overcome the resistance provided by the regulatory T cells (Tregs) due to a decrease in the number of Foxp3-expressing Tregs. Therefore, upregulation and/or maintenance of Tregs during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Here we have undertaken an innovative approach to upregulate Tregs and achieve immunomodulation. RNS60 is a 0.9% saline solution generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. RNS60, but not NS (normal saline), RNS10.3 (TCP-modified saline without excess oxygen) and PNS60 (saline containing excess oxygen without TCP modification), was found to upregulate Foxp3 and enrich Tregs in MBP-primed T cells. Moreover, RNS60, but not NS, RNS10.3 and PNS60, inhibited the production of nitric oxide (NO) and the expression of iNOS in MBP-primed splenocytes. Incubation of the cells with an NO donor abrogated the RNS60-mediated upregulation of Foxp3. These results suggest that RNS60 boosts Tregs via suppression of NO production. Consistent to the suppressive activity of Tregs towards autoreactive T cells, RNS60, but not NS, RNS10.3, or PNS60, suppressed the differentiation of Th17 and Th1 cells and shifted the balance towards a Th2 response. Finally, RNS60 treatment exhibited immunomodulation and ameliorated adoptive transfer of experimental allergic encephalomyelitis, an animal model of MS, via Tregs. These results describe a novel immunomodulatory property of RNS60 and suggest its exploration for therapeutic intervention in MS and other autoimmune disorders. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 71% |
| Kenya | 1 | 14% |
| Unknown | 1 | 14% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 71% |
| Science communicators (journalists, bloggers, editors) | 1 | 14% |
| Scientists | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 64 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Brazil | 1 | 2% |
| Unknown | 63 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 22% |
| Researcher | 13 | 20% |
| Student > Bachelor | 5 | 8% |
| Other | 5 | 8% |
| Student > Master | 5 | 8% |
| Other | 11 | 17% |
| Unknown | 11 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 17% |
| Agricultural and Biological Sciences | 8 | 13% |
| Immunology and Microbiology | 6 | 9% |
| Neuroscience | 5 | 8% |
| Biochemistry, Genetics and Molecular Biology | 4 | 6% |
| Other | 15 | 23% |
| Unknown | 15 | 23% |