The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease
Erdheim-Chester disease (ECD) is a rare histiocytosis, characterized by xanthogranulomatous tissue infiltration by foamy histiocytes. Fibrosis, a histologic hallmark of ECD, is responsible for lesion growth and clinical manifestations. Unraveling molecular fibrotic pathway in ECD would allow the ide...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-07-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1440929 |
| _version_ | 1818133272666832896 |
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| author | Greta Pacini Giulio Cavalli Alessandro Tomelleri Giacomo De Luca Guido Pacini Marina Ferrarini Claudio Doglioni Lorenzo Dagna |
| author_facet | Greta Pacini Giulio Cavalli Alessandro Tomelleri Giacomo De Luca Guido Pacini Marina Ferrarini Claudio Doglioni Lorenzo Dagna |
| author_sort | Greta Pacini |
| collection | DOAJ |
| description | Erdheim-Chester disease (ECD) is a rare histiocytosis, characterized by xanthogranulomatous tissue infiltration by foamy histiocytes. Fibrosis, a histologic hallmark of ECD, is responsible for lesion growth and clinical manifestations. Unraveling molecular fibrotic pathway in ECD would allow the identification of new pharmacologic targets. In this study, we evaluated serum and tissue samples from a large cohort of ECD patients focusing on two major pro-fibrotic mediators, TGF-β1 and chemokine ligand 18 (CCL18). We found a marked increase in CCL18 but not TGF-β1 levels in serum and lesions of ECD patients (p < 0.001), independently of treatment status and consistently over time. Using a linear mathematical model, we also found that elevated CCL18 serum levels correlate with both number and severity of disease localizations. These findings suggest the involvement of CCL18-induced fibrosis in ECD pathogenesis, providing a rationale for exploring CCL18 inhibition as a treatment for progressive fibrosis in ECD. |
| first_indexed | 2024-12-11T08:50:05Z |
| format | Article |
| id | doaj.art-4b1656190b0143879fe67ee02bfdb16f |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-11T08:50:05Z |
| publishDate | 2018-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-4b1656190b0143879fe67ee02bfdb16f2022-12-22T01:14:02ZengTaylor & Francis GroupOncoImmunology2162-402X2018-07-017710.1080/2162402X.2018.14409291440929The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester diseaseGreta Pacini0Giulio Cavalli1Alessandro Tomelleri2Giacomo De Luca3Guido Pacini4Marina Ferrarini5Claudio Doglioni6Lorenzo Dagna7IRCCS San Raffaele Scientific InstituteIRCCS San Raffaele Scientific InstituteIRCCS San Raffaele Scientific InstituteIRCCS San Raffaele Scientific InstituteMax Planck Institute for Molecular GeneticIRCCS San Raffaele Scientific InstituteVita-Salute San Raffaele UniversityIRCCS San Raffaele Scientific InstituteErdheim-Chester disease (ECD) is a rare histiocytosis, characterized by xanthogranulomatous tissue infiltration by foamy histiocytes. Fibrosis, a histologic hallmark of ECD, is responsible for lesion growth and clinical manifestations. Unraveling molecular fibrotic pathway in ECD would allow the identification of new pharmacologic targets. In this study, we evaluated serum and tissue samples from a large cohort of ECD patients focusing on two major pro-fibrotic mediators, TGF-β1 and chemokine ligand 18 (CCL18). We found a marked increase in CCL18 but not TGF-β1 levels in serum and lesions of ECD patients (p < 0.001), independently of treatment status and consistently over time. Using a linear mathematical model, we also found that elevated CCL18 serum levels correlate with both number and severity of disease localizations. These findings suggest the involvement of CCL18-induced fibrosis in ECD pathogenesis, providing a rationale for exploring CCL18 inhibition as a treatment for progressive fibrosis in ECD.http://dx.doi.org/10.1080/2162402X.2018.1440929erdheim-chester diseasefibrosisccl-18 |
| spellingShingle | Greta Pacini Giulio Cavalli Alessandro Tomelleri Giacomo De Luca Guido Pacini Marina Ferrarini Claudio Doglioni Lorenzo Dagna The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease OncoImmunology erdheim-chester disease fibrosis ccl-18 |
| title | The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease |
| title_full | The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease |
| title_fullStr | The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease |
| title_full_unstemmed | The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease |
| title_short | The fibrogenic chemokine CCL18 is associated with disease severity in Erdheim-Chester disease |
| title_sort | fibrogenic chemokine ccl18 is associated with disease severity in erdheim chester disease |
| topic | erdheim-chester disease fibrosis ccl-18 |
| url | http://dx.doi.org/10.1080/2162402X.2018.1440929 |
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