| 1. |
- Gunnarsdottir, Frida Björk, et al.
(författare)
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Breast cancer associated CD169(+) macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells
- 2023
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Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- CD169(+) resident macrophages in lymph nodes of breast cancer patients are for unknown reasons associated with a beneficial prognosis. This contrasts CD169(+) macrophages present in primary breast tumors (CD169(+) TAMs), that correlate with a worse prognosis. We recently showed that these CD169(+) TAMs were associated with tertiary lymphoid structures (TLSs) and T-regs in breast cancer. Here, we show that CD169(+) TAMs can be monocyte-derived and express a unique mediator profile characterized by type I IFNs, CXCL10, PGE(2) and inhibitory co-receptor expression pattern. The CD169(+) monocyte-derived macrophages (CD169(+) Mo-M) possessed an immunosuppressive function in vitro inhibiting NK, T and B cell proliferation, but enhanced antibody and IL6 secretion in activated B cells. Our findings indicate that CD169(+) Mo-M in the primary breast tumor microenvironment are linked to both immunosuppression and TLS functions, with implications for future targeted Mo-M therapy.
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| 2. |
- Rydén, Martin, et al.
(författare)
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A human meniscus explant model for studying early events in osteoarthritis development by proteomics
- 2023
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Ingår i: Journal of Orthopaedic Research. - 0736-0266. ; 41:12, s. 2765-2778
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Tidskriftsartikel (refereegranskat)abstract
- Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. We, therefore, sought to establish a human meniscus ex vivo model to study the meniscal response to cytokine treatment using a proteomics approach. Lateral menisci were obtained from five knee-healthy donors. The meniscal body was cut into vertical slices and further divided into an inner (avascular) and outer region. Explants were either left untreated (controls) or stimulated with cytokines. Medium changes were conducted every 3 days up to Day 21 and liquid chromatography–mass spectrometry was performed at all the time points for the identification and quantification of proteins. Mixed-effect linear regression models were used for statistical analysis to estimate the effect of treatments versus control on protein abundance. Treatment by IL1ß increased release of cytokines such as interleukins, chemokines, and matrix metalloproteinases but a limited catabolic effect in healthy human menisci explants. Further, we observed an increased release of matrix proteins (collagens, integrins, prolargin, tenascin) in response to oncostatin M (OSM) + tumor necrosis factor (TNF) and TNF+interleukin-6 (IL6) + sIL6R treatments, and analysis of semitryptic peptides provided additional evidence of increased catabolic effects in response to these treatments. The induced activation of catabolic processes may play a role in osteoarthritis development.
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| 3. |
- Silvério-Alves, Rita, et al.
(författare)
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GATA2 mitotic bookmarking is required for definitive haematopoiesis
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specification. We show that GATA2 remains bound to chromatin throughout mitosis, in contrast to GFI1B and FOS, via C-terminal zinc finger-mediated DNA binding. GATA2 bookmarks a subset of its interphase targets that are co-enriched for RUNX1 and other regulators of definitive haematopoiesis. Remarkably, homozygous mice harbouring the cyclin B1 mitosis degradation domain upstream Gata2 partially phenocopy knockout mice. Degradation of GATA2 at mitotic exit abolishes definitive haematopoiesis at aorta-gonad-mesonephros, placenta and foetal liver, but does not impair yolk sac haematopoiesis. Our findings implicate GATA2-mediated mitotic bookmarking as critical for definitive haematopoiesis and highlight a dependency on bookmarkers for lineage commitment.
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