Cellular and molecular life sciences : CMLS, 2024-12, Vol.81 (1), p.110-110, Article 110
2024
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- Autor(en) / Beteiligte
- Titel
- MDSC-derived S100A8/9 contributes to lupus pathogenesis by promoting TLR7-mediated activation of macrophages and dendritic cells
- Ist Teil von
- Cellular and molecular life sciences : CMLS, 2024-12, Vol.81 (1), p.110-110, Article 110
- Ort / Verlag
- Cham: Springer International Publishing
- Erscheinungsjahr
- 2024
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Toll-like receptors (TLRs), especially TLR7, play an important role in systemic lupus erythematosus (SLE) pathogenesis. However, the regulatory mechanism underlying the abnormal activation of TLR pathways in patients with SLE has not been elucidated. Notably, accumulating evidence indicates that myeloid-derived suppressor cells (MDSCs) are important regulators of inflammation and autoimmune diseases. Compared with healthy control subjects, patients with SLE have a greater proportion of MDSCs among peripheral blood mononuclear cells (PBMCs); however, the effect of MDSCs on TLR7 pathway activation has not been determined. In the present study, lupus MDSCs significantly promoted TLR7 pathway activation in macrophages and dendritic cells (DCs), exacerbating the imiquimod-induced lupus model. RNA-sequencing analysis revealed significant overexpression of S100 calcium-binding protein A8 (S100A8) and S100A9 in MDSCs from diseased MRL/ lpr mice. In vitro and in vivo studies demonstrated that S100A8/9 effectively promoted TLR7 pathway activation and that S100A8/9 deficiency reversed the promoting effect of MDSCs on TLR7 pathway activation in lupus. Mechanistically, MDSC-derived S100A8/9 upregulated interferon gamma (IFN-γ) secretion by macrophages and IFN-γ subsequently promoted TLR7 pathway activation in an autocrine manner. Taken together, these findings suggest that lupus MDSCs promote TLR7 pathway activation and lupus pathogenesis through the S100A8/9-IFN-γ axis. Our study identified an important target for SLE therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1420-682XeISSN: 1420-9071DOI: 10.1007/s00018-024-05155-wTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10907481
- Format
- –
- Schlagworte
- Animals, Autocrine signalling, Autoimmune diseases, Biochemistry, Biomedical and Life Sciences, Biomedicine, Calcium-binding protein, Calgranulin A - metabolism, Calgranulin B - metabolism, Cell activation, Cell Biology, Chronic conditions, Dendritic cells, Dendritic Cells - metabolism, Gene sequencing, Imiquimod, In vivo methods and tests, Leukocytes (mononuclear), Leukocytes, Mononuclear - metabolism, Life Sciences, Lupus, Lupus Erythematosus, Systemic - metabolism, Lupus Erythematosus, Systemic - pathology, Macrophages, Macrophages - metabolism, Mice, Mice, Inbred MRL lpr, Myeloid-Derived Suppressor Cells, Original, Original Article, Pathogenesis, Peripheral blood mononuclear cells, Regulatory mechanisms (biology), Sequence analysis, Suppressor cells, Systemic lupus erythematosus, TLR7 protein, Toll-Like Receptor 7 - genetics, Toll-Like Receptor 7 - metabolism, Toll-like receptors, γ-Interferon