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Special Issue "Advances in the Pathogenesis and Treatment of Immune-Mediated Inflammatory Diseases"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 September 2021).

Special Issue Editors

Dr. Sander W. Tas
E-Mail Website
Guest Editor
Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology and Laboratory for Experimental Immunology, Academic Medical Center/University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Interests: immune-mediated inflammatory diseases; molecular regulation of inflammation; signal transduction; B cells; dendritic cells; endothelial cells/angiogenesis
Dr. Jan Piet van Hamburg
E-Mail Website
Guest Editor
Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology and Laboratory for Experimental Immunology, Academic Medical Center/University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Interests: immune-mediated inflammatory diseases; molecular regulation of inflammation; lymphocytes; stromal cells; NF-κB signaling

Special Issue Information

Dear Colleagues,

This Special Issue will focus on the rapidly evolving field of immune-mediated inflammatory diseases (IMIDs) and the achievements that were made over the last 10 years. With the advent of novel technologies such as single-cell RNA sequencing and state-of-the-art imaging techniques, researchers in our field have made tremendous progress in unraveling the pathogenesis of autoimmune diseases such as rheumatoid arthritis, vasculitis, and systemic lupus erythematosus, as well as autoinflammatory diseases such as spondyloarthritis and fever syndromes. This has also provided new insights into the contribution of specific (subsets of) immune cells and stromal cells to the inflammatory response, as well as the molecular pathways associated with the pathological processes involved. These advances have led to the identification of promising new therapeutic targets for these diseases and paved the way for novel treatments. However, for rare IMIDs, we are far from fully understanding the underlying mechanisms leading to the development and progression of disease, as well as the response to therapy. A better understanding of the molecular and cellular signatures of these diseases may inform us about potential new treatment options that could be explored.

This Special Issue of IJMS will focus on the molecular, cellular, and clinical advances in the pathogenesis and treatment of IMIDs. We will consider original research, review, or methods manuscripts related to this subject and the keywords below.

Dr. Sander W. Tas
Dr. Jan Piet van Hamburg
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • autoimmunity
  • inflammation
  • immune cells
  • stromal cells
  • lymphoid organs
  • inflammatory mediators
  • signal transduction
  • state-of-the-art technology, including (sc)RNAseq and (imaging)CyTOF
  • molecular imaging and advanced microscopy
  • animal models

Published Papers (2 papers)

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Research

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Article
Efficient Neutrophil Activation Requires Two Simultaneous Activating Stimuli
Int. J. Mol. Sci. 2021, 22(18), 10106; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810106 - 18 Sep 2021
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Abstract
Neutrophils are abundantly present in the synovium and synovial fluid of patients suffering from arthritis. Neutrophils can be activated by a multitude of stimuli and the current dogma states that this is a two-step process, consisting of a priming step followed by an [...] Read more.
Neutrophils are abundantly present in the synovium and synovial fluid of patients suffering from arthritis. Neutrophils can be activated by a multitude of stimuli and the current dogma states that this is a two-step process, consisting of a priming step followed by an activation step. Considering that neutrophil activation occurs in an inflammatory environment, where multiple stimuli are present, we argue that a two-step process is highly unlikely. Here, we indeed demonstrate that neutrophils require simultaneous ligation of two different receptors for efficient activation. We isolated human peripheral blood neutrophils and cultured them with various combinations of stimuli (GM-CSF, fMLF, TNF, and LPS). Next, we evaluated essential neutrophil functions, including degranulation and ROS production using flow cytometry, mediator release using ELISA, NETosis by a live cell imaging method, phagocytosis by imaging flow cytometry, and extracellular vesicle (EV) release quantified by high-resolution flow cytometry. Exposure of neutrophils to any combination of stimuli, but not to single stimuli, resulted in significant degranulation, and mediator and EV release. Furthermore, ROS production increased substantially by dual stimulation, yet appeared to be more dependent on the type of stimulation than on dual stimulation. Phagocytosis was induced to its maximum capacity by a single stimulus, while NETosis was not induced by any of the used physiological stimuli. Our data indicate that neutrophil activation is tightly regulated and requires activation by two simultaneous stimuli, which is largely independent of the combination of stimuli. Full article
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Review

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Review
The Germinal Center Milieu in Rheumatoid Arthritis: The Immunological Drummer or Dancer?
Int. J. Mol. Sci. 2021, 22(19), 10514; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910514 - 29 Sep 2021
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Abstract
Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, affecting approximately 1% of the general population. To alleviate symptoms and ameliorate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to [...] Read more.
Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, affecting approximately 1% of the general population. To alleviate symptoms and ameliorate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore, a more profound understanding of the pathophysiology might lead to more effective therapies, or better still, a cure. The presence of autoantibodies in RA indicates that B cells might have a pivotal role in the disease. This concept is further supported by the fact that a diverse antibody response to various arthritis-related epitopes is associated with arthritis development. In this context, attention has focused in recent years on the role of Germinal Centers (GCs) in RA. Since GCs act as the main anatomic location of somatic hypermutations, and, thus, contributing to the diversity and specificity of (auto) antibodies, it has been speculated that defects in germinal center reactions might be crucial in the initiation and maintenance of auto-immune events. In this paper, we discuss current evidence that various processes within GCs can result in the aberrant production of B cells that possess autoreactive properties and might result in the production of RA related autoantibodies. Secondly, we discuss various (pre-)clinical studies that have targeted various GC processes as novel therapies for RA treatment. Full article
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