{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:08:20Z","timestamp":1784268500879,"version":"3.55.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"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 and aims<\/jats:title>\n                    <jats:p>Differentiating neoplastic proliferation from inflammatory fibrosis in peripheral nerve hypertrophy is critical. We report a patient with a neurofibromatosis type 1 (NF1) deletion exhibiting extreme diffuse nerve enlargement and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-like autoimmunity. This study aims to elucidate the underlying endoneurial fibrotic mechanism, specifically focusing on the signaling networks between Schwann cells (SCs) and fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-cell RNA sequencing was performed on a biopsied sural nerve to profile the cellular and transcriptomic landscape. Intercellular interactome and pseudotime trajectory analyses were utilized to map molecular evolution and signaling crosstalk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptomic profiling revealed that SCs\u2014which normally maintain myelin around axons and support peripheral nerve function\u2014were pathologically entrapped in a dedifferentiated state. Serving as a genetic primer, the\n                      <jats:italic>NF1<\/jats:italic>\n                      deletion lowered the threshold for SC reprogramming, a vulnerability that was subsequently unleashed by a severe autoimmune infiltrate consisting of macrophages and T cells. These reprogrammed SCs abandoned myelin-maintaining genes, such as\n                      <jats:italic>MPZ<\/jats:italic>\n                      , to acquire a pro-fibrotic phenotype. Through a coordinated platelet-derived growth factor (PDGF) dual-axis network involving PDGFC-PDGFRA and PDGFD-PDGFRB, the entrapped SCs exclusively secreted PDGF ligands that potently activated endoneurial fibroblasts and vascular mural cells. This persistent paracrine signaling orchestrated excessive extracellular matrix deposition, driving a massive expansion of the endoneurial interstitium and the formation of classic \u201conion bulbs\u201d.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our data suggest that the macroscopic hypertrophic changes observed in this specific clinical presentation may reflect an aberrant, immune-triggered fibrotic cascade\u2014where autoimmune leukocyte infiltration continuously drives stromal overgrowth\u2014complementing rather than entirely precluding the classical RAS\/MAPK-driven neoplastic SC hyperproliferation. Furthermore, within the limitations of this pilot evaluation, characterizing this potential SC-fibroblast crosstalk indicates that the PDGF signaling pathway may warrant further investigation as a candidate translational therapeutic target for refractory hypertrophic neuropathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1862732","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:42:55Z","timestamp":1784266975000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Schwann cell reprogramming and PDGF-driven nerve hypertrophy in an NF1 patient with CIDP-like autoimmunity"],"prefix":"10.3389","volume":"17","author":[{"given":"Fei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqian","family":"Cao","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Huang","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Bai","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University","place":["Suzhou, Jiangsu, 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