Academic Journal
Case Report: Schwann cell reprogramming and PDGF-driven nerve hypertrophy in an NF1 patient with CIDP-like autoimmunity.
| Τίτλος: | Case Report: Schwann cell reprogramming and PDGF-driven nerve hypertrophy in an NF1 patient with CIDP-like autoimmunity. |
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| Συγγραφείς: | Wang F; Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Cao W; Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China., Lu J; Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Huang R; Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China., Bai Y; Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China., Zhang Y; Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China., Wang Z; Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Chen Z; Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Wang Z; Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Jul 17; Vol. 17, pp. 1862732. Date of Electronic Publication: 2026 Jul 17 (Print Publication: 2026). |
| Τύπος έκδοσης: | Case Reports; Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Schwann Cells*/metabolism , Schwann Cells*/pathology , Schwann Cells*/immunology , Platelet-Derived Growth Factor*/metabolism , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating*/immunology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating*/pathology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating*/genetics , Neurofibromatosis 1*/immunology , Neurofibromatosis 1*/genetics , Neurofibromatosis 1*/pathology , Autoimmunity* , Cellular Reprogramming*, Neurofibromin 1/genetics ; Fibroblasts/metabolism ; Humans ; Hypertrophy ; Signal Transduction ; Female ; Male |
| Περίληψη: | Background and Aims: 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. Methods: 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. Results: Transcriptomic profiling revealed that SCs-which normally maintain myelin around axons and support peripheral nerve function-were pathologically entrapped in a dedifferentiated state. Serving as a genetic primer, the NF1 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 MPZ, 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 "onion bulbs". Interpretation: Our data suggest that the macroscopic hypertrophic changes observed in this specific clinical presentation may reflect an aberrant, immune-triggered fibrotic cascade-where autoimmune leukocyte infiltration continuously drives stromal overgrowth-complementing 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. (Copyright © 2026 Wang, Cao, Lu, Huang, Bai, Zhang, Wang, Chen and Wang.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| Contributed Indexing: | Keywords: PDGF signaling pathway; Schwann cell plasticity; chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); hypertrophic neuropathy; neurofibromatosis type (NF1); single-cell transcriptomics |
| Substance Nomenclature: | 0 (Platelet-Derived Growth Factor) 0 (Neurofibromin 1) 0 (NF1 protein, human) |
| Entry Date(s): | Date Created: 20260801 Date Completed: 20260801 Latest Revision: 20260801 |
| Update Code: | 20260802 |
| PubMed Central ID: | PMC13424072 |
| DOI: | 10.3389/fimmu.2026.1862732 |
| PMID: | 42539570 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2026.1862732 |