{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:27:46Z","timestamp":1786429666874,"version":"build-2736575974"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"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>Background<\/jats:title>\n                    <jats:p>Chronic renal allograft dysfunction (CRAD) continues to limit the long-term survival of transplanted kidneys. Inflammatory cell accumulation during the early phase of CRAD may accelerate fibrotic remodeling and graft dysfunction, although the regulatory mechanisms driving this process have not been fully clarified. Interleukin-11 (IL-11) is increasingly recognized as a fibro-inflammatory mediator, but whether miRNA-dependent regulation of IL-11 participates in early CRAD-associated inflammation remains unknown. This study aimed to investigate whether miR-204-5p regulates early inflammatory injury in CRAD by targeting IL-11.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      A rat CRAD model was established by orthotopic renal transplantation, and kidney tissues were collected at 12 weeks post-transplantation to assess early inflammatory and fibrotic changes. IL-11 expression was inhibited\n                      <jats:italic>in vivo<\/jats:italic>\n                      using IL-11-shRNA AAV, and miR-204-5p was overexpressed using mmu-miR-204-5p AAV. Histological staining, immunohistochemistry, RT-qPCR, ELISA, and renal function analyses were performed.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , BUMPT cells were stimulated with TGF-\u03b21 to mimic CRAD-associated early inflammatory and pro-fibrotic responses. IL-11\/IL-11RA signaling was blocked using neutralizing antibodies or siRNA. The ERK1\/2 inhibitor PD98059 was used to assess downstream pathway activation. The direct interaction between miR-204-5p and IL-11 was validated by dual-luciferase reporter assays, and rescue experiments with recombinant IL-11 were performed to determine whether IL-11 mediates the effect of miR-204-5p.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>miR-204-5p attenuates early inflammatory injury in CRAD by directly targeting IL-11 and suppressing IL-11-associated ERK1\/2-NF-\u03baB inflammatory signaling. The miR-204-5p\/IL-11 axis may represent a potential regulatory pathway and therapeutic target for early inflammatory injury in CRAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1764404","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:35:09Z","timestamp":1786426509000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-204-5p attenuates inflammatory infiltration in early-stage chronic renal allograft dysfunction by modulating the IL-11\/ERK1\/2-NF-\u03baB axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Lin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of University of South China","place":["Hengyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China","place":["Hengyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of University of South China","place":["Hengyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Emergency, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of University of South China","place":["Hengyang, 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