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- Harre, U, et al.
(författare)
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Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 6651-
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Tidskriftsartikel (refereegranskat)abstract
- Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss.
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- Engdahl, Cecilia, 1983, et al.
(författare)
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Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: A potential explanation for the increased risk of rheumatoid arthritis in postmenopausal women
- 2018
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rheumatoid arthritis (RA) preferentially affects women, with the peak incidence coinciding with estrogen decrease in menopause. Estrogen (E2) may therefore have intrinsic immune-regulatory properties that vanish with menopause. Fc sialylation is a crucial factor determining the inflammatory effector function of antibodies. We therefore analyzed whether E2 affects immunoglobulin G (IgG) sialylation. Methods: Postmenopausal (ovariectomized) mice were immunized with ovalbumin and treated with E2 or vehicle. Total and ovalbumin-specific IgG concentrations, sialylation, and Fcγ receptor expression were analyzed. Postmenopausal women with RA receiving hormone replacement therapy, including E2, or no treatment were analyzed for IgG sialylation. Furthermore, effects of E2 on the expression of the sialylation enzyme β-galactoside α2,6-sialyltransferase 1 (St6Gal1) were studied in mouse and human antibody-producing cells. Results: E2 treatment significantly increased Fc sialylation of total and ovalbumin-specific IgG in postmenopausal mice. Furthermore, E2 led to increased expression of inhibitory Fcγ receptor IIb on bone marrow leukocytes. Treatment with E2 also increased St6Gal1 expression in mouse and human antibody-producing cells, providing a mechanistic explanation for the increase in IgG-Fc sialylation. In postmenopausal women with RA, treatment with E2 significantly increased the Fc sialylation of IgG. Conclusions: E2 induces anti-inflammatory effector functions in IgG by inducing St6Gal1 expression in antibody-producing cells and by increasing Fc sialylation. These observations provide a mechanistic explanation for the increased risk of RA in conditions with low estrogen levels such as menopause. © 2018 The Author(s).
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- Ricci, C., et al.
(författare)
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A hard X-ray view of luminous and ultra-luminous infrared galaxies in GOALS - I. AGN obscuration along the merger sequence
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 506:4, s. 5935-5950
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Tidskriftsartikel (refereegranskat)abstract
- The merger of two or more galaxies can enhance the inflow of material from galactic scales into the close environments of active galactic nuclei (AGNs), obscuring and feeding the supermassive black hole (SMBH). Both recent simulations and observations of AGN in mergers have confirmed that mergers are related to strong nuclear obscuration. However, it is still unclear how AGN obscuration evolves in the last phases of the merger process. We study a sample of 60 luminous and ultra-luminous IR galaxies (U/LIRGs) from the GOALS sample observed by NuSTAR. We find that the fraction of AGNs that are Compton thick (CT;N-H >= 10(24)cm(-2) ) peaks at at a late merger stage, prior to coalescence, when the nuclei have projected separations (d(sep)) of 0.4-6 kpc. A similar peak is also observed in the median N-H [[(1.6 +/- 0.5) x 10(24) cm(-2)].]. The vast majority (85(-9)(+7) per cent)) of the AGNs in the final merger stages (d(sep) less than or similar to 10 kpc) are heavily obscured (N-H = 10(23) cm(-2)), and the median N-H of the accreting SMBHs in our sample is systematically higher than that of local hard X-ray-selected AGN, regardless of the merger stage. This implies that these objects have very obscured nuclear environments, with the gas almost completely covering the AGN in late mergers. CT AGNs tend to have systematically higher absorption-corrected X-ray luminosities than less obscured sources. This could either be due to an evolutionary effect, with more obscured sources accreting more rapidly because they have more gas available in their surroundings, or to a selection bias. The latter scenario would imply that we are still missing a large fraction of heavily obscured, lower luminosity (L2-10 less than or similar to 10(43) erg s(-1)) AGNs in U/LIRGs.
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