Leukocytes in Inflammation, Resolution of Inflammation, Autoimmune Diseases and Cancer—Series 2

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 5065

Special Issue Editor

Maisonneuve-Rosemont Hospital, Department of Pathology and Cell Biology, University of Montreal, Montreal, QC H1T 2M4, Canada
Interests: innate immunity; inflammation/resolution of inflammation; acute-phase proteins; leukocyte biology; cardiovascular diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute inflammation is a protective, self-limited mechanism to eliminate invading pathogens and restore homeostasis. Uncontrolled or non-resolving inflammation is a prominent component of many common diseases such as cardiovascular, pulmonary, immune and neurodegenerative diseases, metabolic syndromes, diabetes, and cancer. Since the inflammatory response is critical for survival, the current anti-inflammatory therapies have limitations and often do not lead to repair of affected tissues. Hence, it is critical to appreciate mechanism that control the inflammatory reactions and orchestrate the resolution. Advanced techniques, such as intravital microscopy, single cell sequencing, genetic fate mapping and metabolomics, have driven considerable research in the field, spawning studies into more complex interactions. 

This Special Issue will address inflammatory cell heterogeneity and fate within the inflammatory locus and characterize novel mechanisms (for example, NETosis, reverse migration, transcriptional burst, efferocytosis, microbiota regulation of leukocyte functions) that shape the diverse roles of leukocyte subsets in acute and chronic inflammatory conditions with an emphasis how these mechanisms can be harnessed for development of novel therapeutic approaches. 

Prof. Dr. János G. Filep
Guest Editor

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Keywords

  • neutrophil heterogeneity
  • macrophage subsets
  • NET formation
  • inflammation
  • resolution of inflammation
  • adaptive immunity
  • cardiovascular and pulmonary diseases
  • neurodegenerative diseases
  • autoimmune diseases
  • cancer

Related Special Issue

Published Papers (4 papers)

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Research

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19 pages, 5566 KiB  
Article
Fecal Supernatants from Patients with Crohn’s Disease Induce Inflammatory Alterations in M2 Macrophages and Fibroblasts
Cells 2024, 13(1), 60; https://doi.org/10.3390/cells13010060 - 27 Dec 2023
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Abstract
Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn’s disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, [...] Read more.
Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn’s disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGFβ superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD. Full article
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10 pages, 3062 KiB  
Communication
CD45RA and CD45RO Are Regulated in a Cell-Type Specific Manner in Inflammation and Sepsis
Cells 2023, 12(14), 1873; https://doi.org/10.3390/cells12141873 - 17 Jul 2023
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Abstract
CD45 is a transmembrane glycoprotein that is located on the surface of all leukocytes and modulates both innate and adaptive immune system functions. In a recent study, inflammation modulated the CD45 expression in leukocytes, but the effect on the expression of CD45 subtypes [...] Read more.
CD45 is a transmembrane glycoprotein that is located on the surface of all leukocytes and modulates both innate and adaptive immune system functions. In a recent study, inflammation modulated the CD45 expression in leukocytes, but the effect on the expression of CD45 subtypes is unknown. In the present study, we therefore investigated the effect of inflammatory conditions in humans (surgery, sepsis) and ex vivo incubation with lipopolysaccharides (LPS) on the expression of the subtypes CD45RA and CD45RO in granulocytes, lymphocytes, and monocytes. Whole blood samples were obtained from healthy volunteers, postoperative patients, and patients with sepsis at day 1 of diagnosis, respectively. Samples were incubated with fluorescent antibodies directed against CD45, CD45RA and CD45RO in the absence and presence of lipopolysaccharide and subjected to flow cytometry. In comparison to volunteers, CD45RA surface expression in postoperative and septic patients was reduced by 89% exclusively on granulocytes, but not on lymphocytes or monocytes. In contrast, CD45RO was exclusively reduced on lymphocytes, by 82%, but not on other cell types. Receiver operating characteristic curve analyses demonstrated that CD45RA (on granulocytes) and CD45RO (on lymphocytes) allow a good differentiation of volunteers and patients with sepsis (AUC = 0.9; p = 0.0001). The addition of LPS to the whole blood samples obtained from volunteers, postoperative patients, and septic patients markedly increased the CD45RO expression in granulocytes, lymphocytes, and monocytes. In contrast, LPS reduced CD45RA exclusively on monocytes. In conclusion, the surface expression of CD45RA and CD45RO is regulated in inflammation in a cell-type- and stimulus-specific manner. Considering that CD45 subtypes are critically involved in immune system signaling, the pathophysiologic and diagnostic implications warrant further investigation. Full article
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18 pages, 3860 KiB  
Article
CD301b+ Macrophages as Potential Target to Improve Orthodontic Treatment under Mild Inflammation
Cells 2023, 12(1), 135; https://doi.org/10.3390/cells12010135 - 29 Dec 2022
Cited by 3 | Viewed by 1526
Abstract
Due to improvements of quality of life and the demand for aesthetics, more and more people are choosing orthodontic treatments, resulting in a surge in adult orthodontic patients in recent years. However, a large amount of clinical evidence shows that many orthodontic patients [...] Read more.
Due to improvements of quality of life and the demand for aesthetics, more and more people are choosing orthodontic treatments, resulting in a surge in adult orthodontic patients in recent years. However, a large amount of clinical evidence shows that many orthodontic patients have mild periodontitis in the periodontal tissues, which affects the efficacy of the orthodontic treatment or aggravates the periodontal condition. Therefore, it is important to identify the key factors that affect orthodontic treatments in this inflammatory environment. The aim of this study was to investigate the role of macrophages in orthodontic treatments under inflammatory environments. By analyzing the functional groups of macrophages in the orthodontic rat model of periodontitis, we found that macrophages with high expression levels of CD301b could improve the periodontal microenvironment and improve the efficiency of the orthodontic tooth movement. CD301b+ macrophages transplanted into the model can promote osteogenesis around orthodontic moving teeth, improve bone remodeling during orthodontic treatment, and accelerate orthodontic tooth movement. Considered together, these results suggest that CD301b+ macrophages may play an active role in orthodontic treatments in inflammatory environments and may serve as potential regulatory targets. Full article
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Review

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16 pages, 1418 KiB  
Review
Ophthalmological Manifestations in Inflammatory Bowel Diseases: Keep an Eye on It
Cells 2024, 13(2), 142; https://doi.org/10.3390/cells13020142 - 12 Jan 2024
Viewed by 766
Abstract
Background and aims: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not [...] Read more.
Background and aims: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn’s disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. Methods: PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. Results: The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs’ pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs. Full article
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