{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T06:01:33Z","timestamp":1781157693084,"version":"3.54.1"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"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>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>miR-155 regulates diverse inflammatory responses; however, its role in neurotropic virus\u2013induced CNS inflammation, particularly in specific immune cell subsets, remains unclear. This study aimed to identify the immune cell population in which miR-155 is required for protection against Japanese encephalitis virus (JEV) and to elucidate the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Conditional miR-155 knockout mice with cell type\u2013specific deletion in myeloid cells, dendritic cells (DCs), T cells, or B cells were generated using Cre\u2013LoxP technology. Following JEV infection, we assessed survival, viral burden, type I interferon responses, M1 macrophage polarization, and NLRP3 inflammasome activation. Downstream targets of miR-155 and the effects of NLRP3 inhibition or IL-1\u03b1\/IL-1\u03b2 neutralization were also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Myeloid cell\u2013specific deletion of miR-155, but not its deletion in other immune cell types, significantly increased susceptibility to JEV infection and exacerbated neuroinflammation. This phenotype was associated with elevated viral burdens in both lymphoid and CNS tissues, impaired type I interferon responses, defective M1 macrophage polarization, and reduced NLRP3 inflammasome activation. Mechanistically, Peli1, Jarid2, and Bcl6 were identified as key downstream targets of miR-155 that regulate M1 polarization and inflammasome activity. Furthermore, pharmacological inhibition of NLRP3 or neutralization of IL-1\u03b1 and IL-1\u03b2 further worsened disease severity and suppressed M1 polarization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that miR-155 in myeloid cells, particularly macrophages, is essential for orchestrating protective immune responses during neurotropic virus\u2013induced CNS inflammation by promoting M1 macrophage polarization and NLRP3 inflammasome activation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1818106","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:48:50Z","timestamp":1781156930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Myeloid miR-155 deficiency exacerbates viral encephalitis by hindering M1 macrophage polarization due to impaired NLRP3 inflammasome activation in extraneural tissues"],"prefix":"10.3389","volume":"17","author":[{"given":"Hee Won","family":"Byeon","sequence":"first","affiliation":[{"name":"Bio-Safety Research Institute, and Core Facility Center for Zoonosis Research (Core-FCZR), College of Veterinary Medicine, Jeonbuk National University","place":["Iksan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Bio-Safety Research Institute, and Core Facility Center for Zoonosis Research (Core-FCZR), College of Veterinary Medicine, Jeonbuk National University","place":["Iksan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Won","family":"Cho","sequence":"additional","affiliation":[{"name":"Bio-Safety Research Institute, and Core Facility Center for Zoonosis Research (Core-FCZR), College of Veterinary Medicine, Jeonbuk 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