{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:44:45Z","timestamp":1791319485698,"version":"4.3.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Demyelinating disease of the central nervous system is one of the most common neurological diseases and effective treatment is still under in-depth research. Our previous study showed that <jats:italic>Angiostrongylus cantonensis<\/jats:italic> infection can induce demyelination injury in mouse brains and IL-17A expression was shown to be significantly increased during this process. Moreover, we found that IL-17A inhibition attenuated the demyelination caused by <jats:italic>A. cantonensis<\/jats:italic> infection. However, the underlying mechanisms have not yet been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IL-17A neutralizing antibodies were injected into <jats:italic>A. cantonensis<\/jats:italic> infected mice to decrease IL-17A levels. The activation of glial cells in the brain and the expression of cell markers were detected by a variety of methods, including real-time quantitative PCR, western blotting, and immunofluorescence staining. The relationship between IL-17A and astrocyte activation was further identified by <jats:italic>in vitro<\/jats:italic> experiments. The role of SOCS3 in the IL-17A stimulating process was determined using RNA-seq data collection of infected mice and the siRNA interference method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Demyelination of the corpus callosum was relieved after administration of IL-17A neutralizing antibody and this was accompanied by decreased activation of A1 type astrocytes around this region. The expression of SOCS3 was attenuated and activation of astrocytes by IL-17A was mediated by the IL-17RA\/STAT3\/SOCS3 pathway. IL-17A not only directly damaged oligodendrocytes but also indirectly damaged oligodendrocytes through A1 astrocyte mediation. Specific siRNA inhibition of IL-17A-inducible SOCS3 in astrocytes alleviated their damaging effects on oligodendrocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IL-17A plays an important role in demyelination induced by <jats:italic>A. cantonensis<\/jats:italic> infection <jats:italic>via<\/jats:italic> the IL-17RA\/STAT3\/SOCS3 pathway in A1-type astrocytes, indicating that specific blockage of IL-17A and SOCS3 activity could be a therapeutic strategy for neuroinflammatory demyelinating diseases associated with astrocyte activation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.845011","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T05:23:36Z","timestamp":1646025816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["IL-17A Mediates Demyelination by Activating A1 Astrocytes via SOCS3 During Angiostrongylus cantonensis Infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Zongpu","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-015-4849-5","article-title":"Angiostrongylus Cantonensis in the Vector Snails Pomacea Canaliculata and Achatina Fulica in China: A Meta-Analysis","volume":"115","author":"Song","year":"2016","journal-title":"Parasitol Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(08)70229-9","article-title":"Human Angiostrongyliasis","volume":"8","author":"Wang","year":"2008","journal-title":"Lancet Infect Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1976.25.233","article-title":"Clinical Observations on Eosinophilic Meningitis and Meningoencephalitis Caused by Angiostrongylus Cantonensis on Taiwan","volume":"25","author":"Yii","year":"1976","journal-title":"Am J Trop Med Hyg"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4038\/cmj.v50i2.1577","article-title":"A Case of Eosinophilic Meningitis Following Monitor Lizard Meat Consumption, Exacerbated by Anthelminthics","volume":"50","author":"Hidelaratchi","year":"2005","journal-title":"Ceylon Med J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3347\/kjp.2017.55.3.267","article-title":"Neuronal Apoptosis: Pathological Basis of Behavioral Dysfunctions Induced by Angiostrongylus Cantonensis in Rodents Model","volume":"55","author":"Luo","year":"2017","journal-title":"Korean J Parasitol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-015-4541-9","article-title":"Microglia Activation: One of the Checkpoints in the CNS Inflammation Caused by Angiostrongylus Cantonensis Infection in Rodent Model","volume":"114","author":"Wei","year":"2015","journal-title":"Parasitol Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000608","article-title":"CNS-Disseminated Angiostrongylus Cantonensis Mimicking Atypical Demyelinating Disease","volume":"6","author":"Long","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B8","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.vetpar.2010.03.019","article-title":"Alterations of Myelin Proteins in Inflammatory Demyelination of BALB\/c Mice Caused by Angiostrongylus Cantonensis","volume":"171","author":"Lin","year":"2010","journal-title":"Vet Parasitol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3513651","DOI":"10.1155\/2017\/3513651","article-title":"Inhibiting Interleukin 17 Can Ameliorate the Demyelination Caused by A. 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