Friends or Foes: Innate Immune Cells and Soluble Mediators in Mucosal Inflammation

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

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 8801

Special Issue Editors

Department of Pulmonary Medicine, Erasmus MC Rotterdam PO Box 2040, NL 3000 CA Rotterdam, The Netherlands
Interests: asthma; autoimmunity; BTK; epigenetics; immune signaling; lymphocytes
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1. Department of Pulmonary Medicine, Erasmus MC Rotterdam PO Box 2040, NL 3000 CA Rotterdam, The Netherlands
2. Department of Cell Biology, Erasmus MC Rotterdam PO Box 2040, NL 3000 CA Rotterdam, The Netherlands
Interests: lymphocytes,; neutrophils; chemokines; leukocyte migration; immunological memory; auto-inflammation & autoimmunity

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Guest Editor
Department of Pulmonary Medicine, Erasmus MC Rotterdam PO Box 2040, NL 3000 CA Rotterdam, The Netherlands
Interests: lymphocytes; innate lymphoid cells; T cells; inflammatory bowel disease; cytotoxicity; mucosal immunology

Special Issue Information

Dear Colleagues,

Mucosal barrier tissues—such as the lungs and intestines—are the first contact sites for potentially harmful substances present in the external environment. These complex cellular landscapes are tasked with maintaining tissue homeostasis by tolerating harmless (self)antigens while eliminating pathogenic threats.

Optimal host protection at mucosal surfaces initially depends on dynamic cooperation between epithelial cells and dedicated innate immune cells. Epithelial cells form the first line of defense by providing a physical and biochemical barrier. Resident innate immune cells, including dendritic cells and macrophages, act as sentinels by sensing pathogen- or danger-associated signals. Following activation, they secrete an array of soluble factors, including cytokines, chemokines and growth factors, that act in concert with epithelium-derived mediators to activate innate lymphoid cells (ILCs) and recruit neutrophils and monocytes into the tissue. Instructed by the local cytokine and chemokine milieu, innate immune cells not only activate the adaptive arm to provide a specific long-lasting response, but also directly contribute to pathogen elimination and are involved in regaining tissue homeostasis after pathogen clearance.

Correct fine-tuning of mucosal immune responses is vital for health, as intrinsic defects in innate immune mechanisms feed into susceptibility to infections or malignancies, whereas excessive activation may cause chronic inflammation and tissue damage.

With this Special Issue, we wish to provide new insights into the role of innate immune cells and soluble mediators such as cytokines and chemokines in mucosal immunology in health and disease. We invite you to contribute original research articles, reviews or shorter perspective articles related to this topic.

Dr. Rudi Hendriks
Dr. Mieke Metzemaekers
Dr. Lisette Krabbendam
Guest Editors

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Keywords

  • innate immunity
  • mucosal immunology
  • homeostasis
  • inflammation
  • cytokines
  • chemokines
  • innate leukocytes

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Published Papers (3 papers)

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Research

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28 pages, 5896 KiB  
Article
The Impact of Phase-Specific Macrophage Depletion on Intestinal Anastomotic Healing
by Maximiliane Winter, Barbara Heitplatz, Nils Koppers, Annika Mohr, Alexander D. Bungert, Mazen A. Juratli, Benjamin Strücker, Georg Varga, Andreas Pascher and Felix Becker
Cells 2023, 12(7), 1039; https://doi.org/10.3390/cells12071039 - 29 Mar 2023
Cited by 3 | Viewed by 2397
Abstract
Intestinal anastomotic healing (AH) is critical in colorectal surgery, since disruptive AH leads to anastomotic leakage, a feared postoperative complication. Macrophages are innate immune cells and are instrumental in orchestrating intestinal wound healing, displaying a functional dichotomy as effectors of both tissue injury [...] Read more.
Intestinal anastomotic healing (AH) is critical in colorectal surgery, since disruptive AH leads to anastomotic leakage, a feared postoperative complication. Macrophages are innate immune cells and are instrumental in orchestrating intestinal wound healing, displaying a functional dichotomy as effectors of both tissue injury and repair. The aim of this study was to investigate the phase-specific function and plasticity of macrophages during intestinal AH. Transgenic CD11b diphtheria toxin receptor (CD11b-DTR) mice were used to deplete intestinal macrophages in a temporally controlled manner. Distal colonic end-to-end anastomoses were created in CD11b-DTR, and wild-type mice and macrophages were selectively depleted during either the inflammatory (day 0–3), proliferative (day 4–10), or reparative (day 11–20) phase of intestinal AH, respectively. For each time point, histological and functional analysis as well as gene set enrichment analysis (GSEA) of RNA-sequencing data were performed. Macrophage depletion during the inflammatory phase significantly reduced the associated inflammatory state without compromising microscopic AH. When intestinal macrophages were depleted during the proliferative phase, AH was improved, despite significantly reduced perianastomotic neoangiogenesis. Lastly, macrophages were depleted during the reparative phase and GSEA revealed macrophage-dependent pathways involved in collagen remodeling, cell proliferation, and extracellular matrix composition. However, AH remained comparable at this late timepoint. These results demonstrate that during intestinal AH, macrophages elicit phase-specific effects, and that therapeutic interventions must critically balance their dual and timely defined role. Full article
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16 pages, 5593 KiB  
Article
A BET Protein Inhibitor Targeting Mononuclear Myeloid Cells Affects Specific Inflammatory Mediators and Pathways in Crohn’s Disease
by Ahmed M. I. Elfiky, Ishtu L. Hageman, Marte A. J. Becker, Jan Verhoeff, Andrew Y. F. Li Yim, Vincent W. Joustra, Lieven Mulders, Ivan Fung, Inmaculada Rioja, Rab K. Prinjha, Nicholas N. Smithers, Rebecca C. Furze, Palwinder K. Mander, Matthew J. Bell, Christianne J. Buskens, Geert R. D’Haens, Manon E. Wildenberg and Wouter J. de Jonge
Cells 2022, 11(18), 2846; https://doi.org/10.3390/cells11182846 - 12 Sep 2022
Cited by 3 | Viewed by 3085
Abstract
Background: Myeloid cells are critical determinants of the sustained inflammation in Crohn’s Disease (CD). Targeting such cells may be an effective therapeutic approach for refractory CD patients. Bromodomain and extra-terminal domain protein inhibitors (iBET) are potent anti-inflammatory agents; however, they also possess [...] Read more.
Background: Myeloid cells are critical determinants of the sustained inflammation in Crohn’s Disease (CD). Targeting such cells may be an effective therapeutic approach for refractory CD patients. Bromodomain and extra-terminal domain protein inhibitors (iBET) are potent anti-inflammatory agents; however, they also possess wide-ranging toxicities. In the current study, we make use of a BET inhibitor containing an esterase sensitive motif (ESM-iBET), which is cleaved by carboxylesterase-1 (CES1), a highly expressed esterase in mononuclear myeloid cells. Methods: We profiled CES1 protein expression in the intestinal biopsies, peripheral blood, and CD fistula tract (fCD) cells of CD patients using mass cytometry. The anti-inflammatory effect of ESM-iBET or its control (iBET) were evaluated in healthy donor CD14+ monocytes and fCD cells, using cytometric beads assay or RNA-sequencing. Results: CES1 was specifically expressed in monocyte, macrophage, and dendritic cell populations in the intestinal tissue, peripheral blood, and fCD cells of CD patients. ESM-iBET inhibited IL1β, IL6, and TNFα secretion from healthy donor CD14+ monocytes and fCD immune cells, with 10- to 26-fold more potency over iBET in isolated CD14+ monocytes. Transcriptomic analysis revealed that ESM-iBET inhibited multiple inflammatory pathways, including TNF, JAK-STAT, NF-kB, NOD2, and AKT signaling, with superior potency over iBET. Conclusions: We demonstrate specific CES1 expression in mononuclear myeloid cell subsets in peripheral blood and inflamed tissues of CD patients. We report that low dose ESM-iBET accumulates in CES1-expressing cells and exerts robust anti-inflammatory effects, which could be beneficial in refractory CD patients. Full article
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Review

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12 pages, 701 KiB  
Review
Tuft Cells: Detectors, Amplifiers, Effectors and Targets in Parasite Infection
by Marta Campillo Poveda, Collette Britton, Eileen Devaney, Tom N. McNeilly, François Gerbe, Philippe Jay and Rick M. Maizels
Cells 2023, 12(20), 2477; https://doi.org/10.3390/cells12202477 - 18 Oct 2023
Cited by 2 | Viewed by 2711
Abstract
Tuft cells have recently emerged as the focus of intense interest following the discovery of their chemosensory role in the intestinal tract, and their ability to activate Type 2 immune responses to helminth parasites. Moreover, they populate a wide range of mucosal tissues [...] Read more.
Tuft cells have recently emerged as the focus of intense interest following the discovery of their chemosensory role in the intestinal tract, and their ability to activate Type 2 immune responses to helminth parasites. Moreover, they populate a wide range of mucosal tissues and are intimately connected to immune and neuronal cells, either directly or through the release of pharmacologically active mediators. They are now recognised to fulfil both homeostatic roles, in metabolism and tissue integrity, as well as acting as the first sensors of parasite infection, immunity to which is lost in their absence. In this review we focus primarily on the importance of tuft cells in the intestinal niche, but also link to their more generalised physiological role and discuss their potential as targets for the treatment of gastrointestinal disorders. Full article
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