Increased Levels of STAT1 Protein in Blood CD4 T Cells from Systemic Lupus Erythematosus Patients Are Associated with Perturbed Homeostasis of Activated CD45RA-FOXP3hi Regulatory Subset and Follow-Up Disease Severity
| Autor: | Aleš Goropevšek, Maksimiljan Gorenjak, Radovan Hojs, Ivan Krajnc, Artur Pahor, Suzana Gradišnik, Klara Dai, Tadej Avcin, Iztok Holc |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
biology medicine.diagnostic_test Immunology JAK-STAT signaling pathway FOXP3 Cell Biology medicine.disease Flow cytometry 03 medical and health sciences 030104 developmental biology immune system diseases Interferon Virology Rheumatoid arthritis medicine biology.protein Proliferation Marker STAT1 skin and connective tissue diseases Homeostasis medicine.drug |
| Zdroj: | Journal of Interferon & Cytokine Research. 37:254-268 |
| ISSN: | 1557-7465 1079-9907 |
| Popis: | In murine systemic lupus erythematosus (SLE), aberrant regulation of interferon (IFN)-alpha-STAT1 signaling and perturbed homeostasis of CD4+FOXP3+ regulatory T cells (Tregs) were described. In the present study, STAT1 signaling and circulating Treg subsets were assessed by flow cytometry in 39 SLE patients and their potential association with disease course was examined during long-term follow-up. Levels of STAT1 protein as measured by median fluorescence intensity (MFI) were significantly increased in SLE CD4 T cells when compared with rheumatoid arthritis patients and healthy controls and were positively correlated with disease activity. The highest STAT1 MFI was found in CD45RA-FOXP3hi-activated Treg (aTreg) subset, which demonstrated the highest STAT1 phosphorylation responses among SLE CD4 T cells and significant decrease in proliferation marker Ki-67 expression after IFN-alpha stimulation. Percentage of Ki-67+ aTregs was significantly decreased in SLE patients and was negatively correlated with CD4 T cell STAT1 MFI. A subgroup of SLE patients characterized by lower aTreg counts experienced more severe relapsing disease course during 1,000 days of follow-up. Mean CD4 T cell STAT1 MFI in follow-up samples from SLE patients was negatively correlated with mean of follow-up aTreg counts. Our findings indicate that augmented STAT1 signaling may be involved in perturbed aTreg homeostasis, which could represent a possible marker of SLE disease severity. |
| Databáze: | OpenAIRE |
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