مؤتمر
B7H3-dependent myeloid-derived suppressor cell recruitment and activation in pulmonary fibrosis (poster)
| العنوان: | B7H3-dependent myeloid-derived suppressor cell recruitment and activation in pulmonary fibrosis (poster) |
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| المؤلفون: | Liu, Tianju, Rinke, Andrew E, Santos, Francina Gonzalez De Los, Fang, Chuling, Flaherty, Kevin R, Phan, Sem H |
| بيانات النشر: | Frontiers |
| سنة النشر: | 2023 |
| المجموعة: | University of Michigan: Deep Blue |
| مصطلحات موضوعية: | B7H3, TERT, fibrosis, lung, myeloid-derived suppressor cell (MDSC), Animals, Bleomycin, Idiopathic Pulmonary Fibrosis, Inflammation, Mice, Myeloid-Derived Suppressor Cells |
| جغرافية الموضوع: | San Francisco, CA |
| الوصف: | Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease without effective curative therapy. Recent evidence shows increased circulating myeloid-derived suppressor cells (MDSCs) in cancer, inflammation, and fibrosis, with some of these cells expressing B7H3. We sought to investigate the role of MDSCs in IPF and its potential mediation via B7H3. Here we prospectively collected peripheral blood samples from IPF patients to analyze for circulating MDSCs and B7H3 expression to assess their clinical significance and potential impact on co-cultured lung fibroblasts and T-cell activation. In parallel, we assess MDSC recruitment and potential B7H3 dependence in a mouse model of pulmonary fibrosis. Expansion of MDSCs in IPF patients correlated with disease severity. Co-culture of soluble B7H3 (sB7H3)-treated mouse monocytic MDSCs (M-MDSCs), but not granulocytic MDSCs (G-MDSCs), activated lung fibroblasts and myofibroblast differentiation. Additionally, sB7H3 significantly enhanced MDSC suppression of T-cell proliferation. Activated M-MDSCs displayed elevated TGFβ and Arg1 expression relative to that in G-MDSCs. Treatment with anti-B7H3 antibodies inhibited bone marrow-derived MDSC recruitment into the bleomycin-injured lung, accompanied by reduced expression of inflammation and fibrosis markers. Selective telomerase reverse transcriptase (TERT) deficiency in myeloid cells also diminished MDSC recruitment associated with the reduced plasma level of sB7H3, lung recruitment of c-Kit+ hematopoietic progenitors, myofibroblast differentiation, and fibrosis. Lung single-cell RNA sequencing (scRNA-seq) revealed fibroblasts as a predominant potential source of sB7H3, and indeed the conditioned medium from activated mouse lung fibroblasts had a chemotactic effect on bone marrow (BM)-MDSC, which was abolished by B7H3 blocking antibody. Thus, in addition to their immunosuppressive activity, TERT and B7H3-dependent MDSC expansion/recruitment from BM could play a paracrine role to activate myofibroblast ... |
| نوع الوثيقة: | conference object |
| وصف الملف: | Electronic-eCollection; application/pdf |
| اللغة: | unknown |
| تدمد: | 1664-3224 |
| العلاقة: | https://www.ncbi.nlm.nih.gov/pubmed/36045668Test; https://hdl.handle.net/2027.42/175996Test; https://dx.doi.org/10.7302/7036Test; Am J Respir Crit Care Med; orcid:0000-0001-7686-0291; 13; 901349; Liu, Tianju; Rinke, Andrew E; Santos, Francina Gonzalez De Los; Fang, Chuling; Flaherty, Kevin R; 0000-0001-7686-0291; Phan, Sem H |
| DOI: | 10.3389/fimmu.2022.901349 |
| DOI: | 10.7302/7036 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2022.901349Test https://doi.org/10.7302/7036Test https://hdl.handle.net/2027.42/175996Test https://www.ncbi.nlm.nih.gov/pubmed/36045668Test |
| حقوق: | Licence for published version: Creative Commons Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.B079878 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16643224 |
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| DOI: | 10.3389/fimmu.2022.901349 |