{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:50Z","timestamp":1789625030856,"version":"build-2803163510"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease characterized by T lymphocyte infiltration and demyelination that can lead to severe disability without treatment. However, effective treatment for MS remains an unmet need. 2\u2032-deoxyinosine (2\u2032-DI), an endogenous nucleoside, has been implicated in tumorigenesis and immune regulation. This study was performed to investigate whether prophylactic 2\u2032-DI intervention could prevent MS progression and elucidate its action mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>2\u2032-DI was administered to experimental autoimmune encephalomyelitis mice in vivo and cultured peripheral blood samples from MS patients in vitro, followed by pathological analysis, body weight monitoring, and disease severity assessment. Furthermore, RNA sequencing and serum metabolomics were conducted to explore the underlying regulatory mechanism of 2\u2032-DI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with healthy controls, MS patients exhibited significantly reduced 2\u2032-DI levels in peripheral blood. Prophylactic administration of 2\u2032-DI could prevent the progression of MS and mitigate inflammatory infiltration in the EAE mouse model. Immunomodulatory studies revealed that 2'-DI could decrease Th1 and Th17 cells, whereas increase Treg and Th2 cells. Moreover, 2\u2032-DI could also promote the expression of anti-inflammatory cytokines and transcription factors while inhibiting the expression of pro-inflammatory cytokines and chemokines. Notably, 2\u2032-DI intervention increased AMPK phosphorylation status, suggesting a potential association between elevated AMPK phosphorylation and the 2\u2032-DI-mediated reversal of Th1\/Th2 and Th17\/Treg cell imbalance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>2\u2032-DI may serve as a promising prophylactic candidate for MS by inhibiting central neuroinflammation and correcting peripheral and central Th1\/Th2 and Th17\/Treg immune imbalance, with its immunomodulatory effects potentially involving AMPK phosphorylation upregulation, thereby alleviating neuroinflammation and neurodegeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1837446","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:33:22Z","timestamp":1789623202000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["2\u2032-deoxyinosine ameliorates multiple sclerosis through modulating Th1\/Th2 and Th17\/Treg cell balance with potential involvement of AMPK phosphorylation"],"prefix":"10.3389","volume":"17","author":[{"given":"Daqing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuchang Central Hospital","place":["Xuchang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University","place":["Kunshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University","place":["Kunshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/s41591-025-04014-w","article-title":"Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis","volume":"32","author":"Abdelhak","year":"2026","journal-title":"Nat. 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