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  1. Article ; Online: Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy.

    Borst, Rowie / Meyaard, Linde / Pascoal Ramos, M Ines

    Journal of translational medicine

    2024  Volume 22, Issue 1, Page(s) 382

    Abstract: Tumors are highly complex and heterogenous ecosystems where malignant cells interact with healthy cells and the surrounding extracellular matrix (ECM). Solid tumors contain large ECM deposits that can constitute up to 60% of the tumor mass. This supports ...

    Abstract Tumors are highly complex and heterogenous ecosystems where malignant cells interact with healthy cells and the surrounding extracellular matrix (ECM). Solid tumors contain large ECM deposits that can constitute up to 60% of the tumor mass. This supports the survival and growth of cancerous cells and plays a critical role in the response to immune therapy. There is untapped potential in targeting the ECM and cell-ECM interactions to improve existing immune therapy and explore novel therapeutic strategies. The most abundant proteins in the ECM are the collagen family. There are 28 different collagen subtypes that can undergo several post-translational modifications (PTMs), which alter both their structure and functionality. Here, we review current knowledge on tumor collagen composition and the consequences of collagen PTMs affecting receptor binding, cell migration and tumor stiffness. Furthermore, we discuss how these alterations impact tumor immune responses and how collagen could be targeted to treat cancer.
    MeSH term(s) Humans ; Neoplasms/therapy ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Collagen/metabolism ; Immunotherapy/methods ; Extracellular Matrix/metabolism ; Animals ; Protein Processing, Post-Translational
    Chemical Substances Collagen (9007-34-5)
    Language English
    Publishing date 2024-04-24
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2118570-0
    ISSN 1479-5876 ; 1479-5876
    ISSN (online) 1479-5876
    ISSN 1479-5876
    DOI 10.1186/s12967-024-05199-3
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  2. Article ; Online: Sensing context: Inhibitory receptors on non-hematopoietic cells.

    von Richthofen, Helen J / Meyaard, Linde

    European journal of immunology

    2023  Volume 53, Issue 5, Page(s) e2250306

    Abstract: Similar to immune cells, non-hematopoietic cells recognize microbial and endogenous threats. Their response to these stimuli is dependent on the environmental context. For example, intact intestinal epithelium expresses pattern recognition receptors ( ... ...

    Abstract Similar to immune cells, non-hematopoietic cells recognize microbial and endogenous threats. Their response to these stimuli is dependent on the environmental context. For example, intact intestinal epithelium expresses pattern recognition receptors (PRRs) but should tolerate commensal bacteria, while damaged epithelium should respond promptly to initiate an immune response. This indicates that non-hematopoietic cells possess mechanisms to sense environmental context and regulate their responses. Inhibitory receptors provide context sensing to immune cells. For instance, they raise the threshold for activation to prevent overzealous immune activation to harmless stimuli. Inhibitory receptors are typically studied on hematopoietic cells, but several of these receptors are expressed on non-hematopoietic cells. Here, we review evidence for the regulation of non-hematopoietic cells by inhibitory receptors, focusing on epithelial and endothelial cells. We explain that inhibitory receptors on these cells can sense a wide range of signals, including cell-cell adhesion, cell-matrix adhesion, and apoptotic cells. More importantly, they regulate various functions on these cells, including immune activation, proliferation, and migration. In conclusion, we propose that inhibitory receptors provide context to non-hematopoietic cells by fine tuning their response to endogenous or microbial stimuli. These findings prompt to investigate the functions of inhibitory receptors on non-hematopoietic cells more systematically.
    MeSH term(s) Endothelial Cells ; Receptors, Pattern Recognition ; Intestinal Mucosa ; Epithelium ; Cell Adhesion
    Chemical Substances Receptors, Pattern Recognition
    Language English
    Publishing date 2023-04-13
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202250306
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  3. Article ; Online: Mechanosensing regulates tissue repair program in macrophages.

    Meizlish, Matthew L / Kimura, Yoshitaka / Pope, Scott D / Matta, Rita / Kim, Catherine / Philip, Naomi H / Meyaard, Linde / Gonzalez, Anjelica / Medzhitov, Ruslan

    Science advances

    2024  Volume 10, Issue 11, Page(s) eadk6906

    Abstract: Tissue-resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of ... ...

    Abstract Tissue-resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a noncanonical, integrin-independent mechanism analogous to amoeboid migration. We find that these cytoskeletal dynamics also integrate biochemical signaling by colony-stimulating factor 1 and ultimately regulate chromatin accessibility to control the mechanosensitive gene expression program. This study identifies an "amoeboid" mode of ECM mechanosensing through which macrophages may regulate tissue repair and fibrosis.
    MeSH term(s) Extracellular Matrix/metabolism ; Macrophages/metabolism ; Cytoskeleton ; Integrins/metabolism ; Signal Transduction
    Chemical Substances Integrins
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adk6906
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  4. Article ; Online: Inhibitory pattern recognition receptors.

    Rumpret, Matevž / von Richthofen, Helen J / Peperzak, Victor / Meyaard, Linde

    The Journal of experimental medicine

    2021  Volume 219, Issue 1

    Abstract: Pathogen- and damage-associated molecular patterns are sensed by the immune system's pattern recognition receptors (PRRs) upon contact with a microbe or damaged tissue. In situations such as contact with commensals or during physiological cell death, the ...

    Abstract Pathogen- and damage-associated molecular patterns are sensed by the immune system's pattern recognition receptors (PRRs) upon contact with a microbe or damaged tissue. In situations such as contact with commensals or during physiological cell death, the immune system should not respond to these patterns. Hence, immune responses need to be context dependent, but it is not clear how context for molecular pattern recognition is provided. We discuss inhibitory receptors as potential counterparts to activating pattern recognition receptors. We propose a group of inhibitory pattern recognition receptors (iPRRs) that recognize endogenous and microbial patterns associated with danger, homeostasis, or both. We propose that recognition of molecular patterns by iPRRs provides context, helps mediate tolerance to microbes, and helps balance responses to danger signals.
    MeSH term(s) Animals ; Disease Susceptibility ; Gene Expression Regulation ; Homeostasis ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immune System/cytology ; Immune System/immunology ; Immune System/metabolism ; Immune Tolerance ; Immunity ; Immunity, Innate ; Inflammation/etiology ; Inflammation/metabolism ; Inflammation/pathology ; Organ Specificity ; Receptors, Pattern Recognition/physiology ; Signal Transduction
    Chemical Substances Receptors, Pattern Recognition
    Language English
    Publishing date 2021-12-14
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20211463
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  5. Article ; Online: VSTM1-v2 does not drive human Th17 cell differentiation: A replication study.

    von Richthofen, Helen J / Hafkamp, Florianne M J / van Haperen, Anouk / de Jong, Esther C / Meyaard, Linde

    PloS one

    2023  Volume 18, Issue 4, Page(s) e0284404

    Abstract: Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human myeloid cells. We previously showed that dendritic cell (DC)-driven Th17 cell differentiation of human naive CD4+ T cells requires presence of ... ...

    Abstract Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human myeloid cells. We previously showed that dendritic cell (DC)-driven Th17 cell differentiation of human naive CD4+ T cells requires presence of neutrophils, which is inhibited by SIRL-1 ligation. VSTM1-v2 is a soluble isoform of SIRL-1, which was previously proposed to function as a Th17 polarizing cytokine. Here, we investigated the effect of VSTM1-v2 on DC-driven Th17 cell development. Neutrophils induced DC-driven Th17 cell differentiation, which was not enhanced by VSTM1-v2. Similarly, we found no effect of VSTM1-v2 on cytokine-driven Th17 cell development. Thus, our results do not support a role for VSTM1-v2 in Th17 cell differentiation.
    MeSH term(s) Humans ; Cell Differentiation ; Cytokines ; Dendritic Cells ; Neutrophils ; Protein Isoforms ; Th17 Cells
    Chemical Substances Cytokines ; Protein Isoforms ; VSTM1 protein, human
    Language English
    Publishing date 2023-04-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0284404
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  6. Article ; Online: LAIR and collagens in immune regulation.

    Meyaard, Linde

    Immunology letters

    2010  Volume 128, Issue 1, Page(s) 26–28

    MeSH term(s) Amino Acid Motifs ; Animals ; Collagen/immunology ; Collagen/metabolism ; Extracellular Matrix ; Gene Expression Regulation ; Humans ; Immunomodulation ; Leukocytes/immunology ; Leukocytes/metabolism ; Receptors, Immunologic/genetics ; Receptors, Immunologic/immunology ; Receptors, Immunologic/metabolism ; Signal Transduction ; Thrombosis/immunology ; Tumor Escape ; src-Family Kinases/metabolism
    Chemical Substances LAIR-2 receptor ; Receptors, Immunologic ; leukocyte-associated immunoglobulin-like receptor 1 ; Collagen (9007-34-5) ; src-Family Kinases (EC 2.7.10.2)
    Language English
    Publishing date 2010-01-18
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 445150-8
    ISSN 1879-0542 ; 0165-2478
    ISSN (online) 1879-0542
    ISSN 0165-2478
    DOI 10.1016/j.imlet.2009.09.014
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    Zs.A 1512: Show issues Location:
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  7. Article ; Online: VSTM1-v2 does not drive human Th17 cell differentiation

    Helen J. von Richthofen / Florianne M. J. Hafkamp / Anouk van Haperen / Esther C. de Jong / Linde Meyaard

    PLoS ONE, Vol 18, Iss

    A replication study

    2023  Volume 4

    Abstract: Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human myeloid cells. We previously showed that dendritic cell (DC)-driven Th17 cell differentiation of human naive CD4+ T cells requires presence of ... ...

    Abstract Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human myeloid cells. We previously showed that dendritic cell (DC)-driven Th17 cell differentiation of human naive CD4+ T cells requires presence of neutrophils, which is inhibited by SIRL-1 ligation. VSTM1-v2 is a soluble isoform of SIRL-1, which was previously proposed to function as a Th17 polarizing cytokine. Here, we investigated the effect of VSTM1-v2 on DC-driven Th17 cell development. Neutrophils induced DC-driven Th17 cell differentiation, which was not enhanced by VSTM1-v2. Similarly, we found no effect of VSTM1-v2 on cytokine-driven Th17 cell development. Thus, our results do not support a role for VSTM1-v2 in Th17 cell differentiation.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: VSTM1-v2 does not drive human Th17 cell differentiation

    Helen J von Richthofen / Florianne M J Hafkamp / Anouk van Haperen / Esther C de Jong / Linde Meyaard

    PLoS ONE, Vol 18, Iss 4, p e

    A replication study.

    2023  Volume 0284404

    Abstract: Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human myeloid cells. We previously showed that dendritic cell (DC)-driven Th17 cell differentiation of human naive CD4+ T cells requires presence of ... ...

    Abstract Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human myeloid cells. We previously showed that dendritic cell (DC)-driven Th17 cell differentiation of human naive CD4+ T cells requires presence of neutrophils, which is inhibited by SIRL-1 ligation. VSTM1-v2 is a soluble isoform of SIRL-1, which was previously proposed to function as a Th17 polarizing cytokine. Here, we investigated the effect of VSTM1-v2 on DC-driven Th17 cell development. Neutrophils induced DC-driven Th17 cell differentiation, which was not enhanced by VSTM1-v2. Similarly, we found no effect of VSTM1-v2 on cytokine-driven Th17 cell development. Thus, our results do not support a role for VSTM1-v2 in Th17 cell differentiation.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Is sex bias orchestrated in the skin?

    Pandit, Aridaman / Meyaard, Linde / Radstake, Timothy R D J

    Nature immunology

    2017  Volume 18, Issue 2, Page(s) 142–143

    Language English
    Publishing date 2017-01-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/ni.3658
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    Zs.A 5294: Show issues Location:
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  10. Article: The inhibitory collagen receptor LAIR-1 (CD305).

    Meyaard, Linde

    Journal of leukocyte biology

    2008  Volume 83, Issue 4, Page(s) 799–803

    Abstract: The immune system protects the body from invaders such as viruses and bacteria. Immune cells must be activated in the correct context to function properly. It is critical that the receptors, costimulatory molecules, and cytokines that orchestrate this ... ...

    Abstract The immune system protects the body from invaders such as viruses and bacteria. Immune cells must be activated in the correct context to function properly. It is critical that the receptors, costimulatory molecules, and cytokines that orchestrate this activation are carefully regulated to prevent uncontrolled inflammation and autoimmunity. Inhibitory receptors play an important role in regulation of immune cell function, usually upon interaction with ligands present on other cells. In contrast, the function of the inhibitory leukocyte-associated Ig-like receptor (LAIR)-1 can be regulated by extracellular matrix collagens. LAIR-1 is expressed on most cells of the immune system, and its function has been studied on multiple cell types. This review summarizes current literature about LAIR-1, a receptor that potentially is able to regulate multiple steps of an immune response.
    MeSH term(s) Cloning, Molecular ; Homeostasis ; Humans ; Killer Cells, Natural/immunology ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Receptors, Collagen/physiology ; Receptors, Immunologic/chemistry ; Receptors, Immunologic/genetics ; Receptors, Immunologic/physiology ; T-Lymphocytes/immunology ; src Homology Domains ; src-Family Kinases
    Chemical Substances Proto-Oncogene Proteins ; Receptors, Collagen ; Receptors, Immunologic ; leukocyte-associated immunoglobulin-like receptor 1 ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; CSK tyrosine-protein kinase (EC 2.7.10.2) ; src-Family Kinases (EC 2.7.10.2) ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 (EC 3.1.3.48)
    Language English
    Publishing date 2008-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1189/jlb.0907609
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