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- Majhi, RK, et al.
(författare)
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Metformin strengthens uroepithelial immunity against E. coli infection
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19263-
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Tidskriftsartikel (refereegranskat)abstract
- Urinary tract infection frequently caused by E. coli is one of the most common bacterial infections. Increasing antibiotic resistance jeopardizes successful treatment and alternative treatment strategies are therefore mandatory. Metformin, an oral antidiabetic drug, has been shown to activate macrophages in the protection against certain infecting microorganisms. Since epithelial cells often form the first line of defense, we here investigated the effect on uroepithelial cells during E. coli infection. Metformin upregulated the human antimicrobial peptides cathelicidin LL-37 and RNase7 via modulation of the TRPA1 channel and AMPK pathway. Interestingly, metformin stimulation enriched both LL-37 and TRPA1 in lysosomes. In addition, metformin specifically increased nitric oxide and mitochondrial, but not cytosolic ROS. Moreover, metformin also triggered mRNA expression of the proinflammatory cytokines IL1B, CXCL8 and growth factor GDF15 in human uroepithelial cells. The GDF15 peptide stimulated macrophages increased LL-37 expression, with increased bacterial killing. In conclusion, metformin stimulation strengthened the innate immunity of uroepithelial cells inducing enhanced extracellular and intracellular bacterial killing suggesting a favorable role of metformin in the host defense.
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- Fuchs, S, et al.
(författare)
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Natural Killer Cells in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - A Review of the Literature
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 796640-
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Tidskriftsartikel (refereegranskat)abstract
- Anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV) is a group of systemic autoimmune diseases characterized by inflammation of small- and medium-sized vessels. The three main types of AAV are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). A growing number of studies focus on natural killer (NK) cells in AAV. NK cells are innate lymphoid cells with important roles in anti-viral and anti-tumor defense, but their roles in the pathogenesis of autoimmunity is less well established. In this review, we will present a summary of what is known about the number, phenotype and function of NK cells in patients with AAV. We review the literature on NK cells in the circulation of AAV patients, studies on tissue resident NK cells and how the treatment affects NK cells.
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- Scheffschick, A, et al.
(författare)
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Kidney infiltrating NK cells and NK-like T-cells in lupus nephritis: presence, localization, and the effect of immunosuppressive treatment
- 2022
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 1365-2249 .- 0009-9104. ; 207:2, s. 199-204
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disease with kidney inflammation, lupus nephritis (LN), being one of the most severe manifestations. Immune complex deposits, particularly in glomeruli, and T cells, B cells, and myeloid cells, mainly with extraglomerular localization, contribute to the inflammatory process. Natural killer (NK) cells have been suggested to play a role in autoimmune diseases, but have not been investigated in detail in renal lupus before. In this exploratory study, we performed the first characterization of NK cell number and distribution in LN kidney biopsies. Twelve SLE patients were analyzed in the active phase of disease and five patients following immunosuppressive therapy. CD56+ cells, corresponding to NK cells or NK-like T-cells, were identified in all patients; however, with reduced numbers in four out of five patients at follow-up. Furthermore, cells were present in the kidney interstitium and peri-glomerular areas, but only rarely in glomeruli. Fluorescent co-staining of CD56 or NKp46 and CD3 revealed the presence of both CD56+/NKp46+CD3-NK cells and CD56+/NKp46+CD3+NK-like T-cells. Compared to healthy kidney sections, one out of four LN patients showed increased numbers of NK cells. A correlation between CD56+ and NK cells with clinical parameters could not be observed, perhaps due to the small patient cohort. In conclusion, we have identified NK cells and NK-like T-cells in the LN kidney and performed the first detailed analysis of their localization during active and inactive diseases. Their role in LN pathogenesis is, however, unclear and deserves further studies.
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