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“IL-33/IL-31 Axis” in Allergic and Immune-Mediated 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 April 2020) | Viewed by 22468

Special Issue Editors


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Guest Editor
Head of Allergology and Clinical Immunology Unit, Department of Internal Medicine, University of Genoa and San Bartolomeo Hospital, Sarzana, Italy
Interests: immunodeficiency; autoimmunity; neuro-endocrino-immunology; pharmacogenomics; soluble molecules; immune-mediated diseases; allergies; vaccines
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
Interests: inflammatory mediators; the citokine network (interleukins, chemokines, adhesion molecules, lipoxines); the oxidative stress in various areas of clinical immunology; allergy; oncology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Clinical Immunology Unit, Department of Internal Medicine, University of Genova and, Ospedale Policlinico San Martino, Genova, Italy
Interests: immune system; autoimmune diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory bowel diseases (IBDs) are characterized by the involvement of Th2 immunity.  Several mediators lead to IgEs production, thus including key cytokines like IL-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine, it regulates cell proliferation, and it is involved in tissue remodeling. IL-33, acting through its receptor ST2L, is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions.

To date, several researchers have been investigated the involvement of IL-31 and IL-33 in several allergic and immune-mediated diseases. Further studies are needed in order to understand the future applications of these molecules as novel therapeutic agents.

In this Special Issue, we will address the role of IL-31 and IL-33, other related-cytokines/receptors, or signaling molecules that play a role in the pathogenesis of allergic and immune-mediated diseases. We will consider all reports, without restrictions in the animal or cellular model used. We encourage researchers to contribute experimental papers or review articles.

Prof. Dr. Giuseppe Murdaca
Assoc. Prof. Sebastiano Gangemi
Dr. Monica Greco
Guest Editors

Manuscript Submission Information

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Keywords

  • IL-31
  • IL-33
  • Allergic diseases
  • Immunologic diseases
  • ASTHMA
  • Food allergy
  • Chronic spontaneous urticaria (CSU)
  • Atopic dermatitis (AD)
  • Systemic lupus erythematosus (SLE)
  • Systemic sclerosis (SSc)
  • Inflammatory bowel diseases (IBDs)

Published Papers (6 papers)

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Editorial

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3 pages, 197 KiB  
Editorial
The IL-33/IL-31 Axis in Allergic and Immune-Mediated Diseases
by Giuseppe Murdaca, Sebastiano Gangemi and Monica Greco
Int. J. Mol. Sci. 2023, 24(11), 9227; https://doi.org/10.3390/ijms24119227 - 25 May 2023
Cited by 2 | Viewed by 821
Abstract
Interleukin 31 (IL-31) belongs to the IL-6 superfamily [...] Full article
(This article belongs to the Special Issue “IL-33/IL-31 Axis” in Allergic and Immune-Mediated Diseases)

Research

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12 pages, 2158 KiB  
Article
House Dust Mite Induces Bone Marrow IL-33-Responsive ILC2s and TH Cells
by Emma Boberg, Kristina Johansson, Carina Malmhäll, Julie Weidner and Madeleine Rådinger
Int. J. Mol. Sci. 2020, 21(11), 3751; https://doi.org/10.3390/ijms21113751 - 26 May 2020
Cited by 9 | Viewed by 2962
Abstract
Type 2 innate lymphoid cells (ILC2s) and their adaptive counterpart type 2 T helper (TH2) cells respond to interleukin-33 (IL-33) by producing IL-5, which is a crucial cytokine for eosinophil development in the bone marrow. The aim of this study was [...] Read more.
Type 2 innate lymphoid cells (ILC2s) and their adaptive counterpart type 2 T helper (TH2) cells respond to interleukin-33 (IL-33) by producing IL-5, which is a crucial cytokine for eosinophil development in the bone marrow. The aim of this study was to determine if bone marrow ILC2s, TH cells, and eosinophils are locally regulated by IL-33 in terms of number and activation upon exposure to the common aeroallergen house dust mite (HDM). Mice that were sensitized and challenged with HDM by intranasal exposures induced eosinophil development in the bone marrow with an initial increase of IL5Rα+ eosinophil progenitors, following elevated numbers of mature eosinophils and the induction of airway eosinophilia. Bone marrow ILC2s, TH2, and eosinophils all responded to HDM challenge by increased IL-33 receptor (ST2) expression. However, only ILC2s, but not TH cells, revealed increased ST2 expression at the onset of eosinophil development, which significantly correlated with the number of eosinophil progenitors. In summary, our findings suggest that airway allergen challenges with HDM activates IL-33-responsive ILC2s, TH cells, and eosinophils locally in the bone marrow. Targeting the IL-33/ST2 axis in allergic diseases including asthma may be beneficial by decreasing eosinophil production in the bone marrow. Full article
(This article belongs to the Special Issue “IL-33/IL-31 Axis” in Allergic and Immune-Mediated Diseases)
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15 pages, 3395 KiB  
Article
Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection
by Yuhan Chang, Yi-min Hsiao, Chih-Chien Hu, Chih-Hsiang Chang, Cai-Yan Li, Steve W. N. Ueng and Mei-Feng Chen
Int. J. Mol. Sci. 2020, 21(8), 2904; https://doi.org/10.3390/ijms21082904 - 21 Apr 2020
Cited by 9 | Viewed by 3558
Abstract
Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint [...] Read more.
Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss. Full article
(This article belongs to the Special Issue “IL-33/IL-31 Axis” in Allergic and Immune-Mediated Diseases)
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Review

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20 pages, 1994 KiB  
Review
The Role of Pro-Inflammatory and Regulatory Signaling by IL-33 in the Brain and Liver: A Focused Systematic Review of Mouse and Human Data and Risk of Bias Assessment of the Literature
by Nika Zharichenko and Dolores B. Njoku
Int. J. Mol. Sci. 2020, 21(11), 3933; https://doi.org/10.3390/ijms21113933 - 30 May 2020
Cited by 5 | Viewed by 3152
Abstract
Interleukin (IL)-33 is a member of the IL-1 family of proteins that have multiple roles in organ-specific inflammation. Many studies suggest diagnostic and therapeutic implications of this cytokine. Many studies have reported pro-inflammatory roles for IL-33 in innate immune responses involving the heart [...] Read more.
Interleukin (IL)-33 is a member of the IL-1 family of proteins that have multiple roles in organ-specific inflammation. Many studies suggest diagnostic and therapeutic implications of this cytokine. Many studies have reported pro-inflammatory roles for IL-33 in innate immune responses involving the heart and lung. Recent studies also describe pro-inflammatory and regulatory roles for IL-33 in the pathogenesis of brain and liver disorders in addition to regulatory roles for this cytokine in the heart and lung. In this focused systematic review, we will review the literature regarding pro-inflammatory and regulatory effects of IL-33 in the brain and liver. We will also assess the potential risk of bias in the published literature in order to uncover gaps in the knowledge that will be useful for the scientific community. We utilized guidelines set by preferred reporting items for systemic reviews and meta-analyses. The electronic database was PubMed. Eligibility criteria included organ-specific inflammation in mice and humans, organ-specific inflammation in the central nervous and hepatic systems, and IL-33. Outcomes were pro-inflammatory or regulatory effects of IL-33. Risk of bias in individual studies and across studies was addressed by adapting the Cochrane Rob 2.0 tool. We discovered that a source of bias across the studies was a lack of randomization in human studies. Additionally, because the majority of studies were performed in mice, this could be perceived as a potential risk of bias. Regarding the central nervous system, roles for IL-33 in the development and maturation of neuronal circuits were reported; however, exact mechanisms by which this occurred were not elucidated. IL-33 was produced by astrocytes and endothelial cells while IL-33 receptors were expressed by microglia and astrocytes, demonstrating that these cells are first responders for IL-33; however, in the CNS, IL-33 seems to induce Th1 cytokines such as IL-1β and TNF-α chemokines such as RANTES, MCP-1, MIP-1α, and IP-10, as well as nitric oxide. In the liver, similar risks of bias were determined because of the lack of randomized controlled trials in humans and because the majority of studies were performed in mice. Interestingly, the strain of mouse utilized in the study seemed to affect the role of IL-33 in liver inflammation. Lastly, similar to the brain, IL-33 appeared to have ST2-independent regulatory functions in the liver. Our results reveal plausible gaps in what is known regarding IL-33 in the pathogenesis of brain and liver disorders. We highlight key studies in the lung and heart as examples of advancements that likely occurred because of countless basic and translational studies in this area. More research is needed in these areas in order to assess the diagnostic or therapeutic potential of IL-33 in these disorders. Full article
(This article belongs to the Special Issue “IL-33/IL-31 Axis” in Allergic and Immune-Mediated Diseases)
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19 pages, 937 KiB  
Review
IL-33/IL-31 Axis in Osteoporosis
by Massimo De Martinis, Maria Maddalena Sirufo, Mariano Suppa and Lia Ginaldi
Int. J. Mol. Sci. 2020, 21(4), 1239; https://doi.org/10.3390/ijms21041239 - 13 Feb 2020
Cited by 42 | Viewed by 5106
Abstract
The study of the immunoskeletal interface has led to the discovery of numerous cytokines involved in the regulation of bone remodeling, providing valuable information on the pathogenesis of osteoporosis. The role of inflammatory cytokines of the Th1 and Th17 profile in osteoporosis is [...] Read more.
The study of the immunoskeletal interface has led to the discovery of numerous cytokines involved in the regulation of bone remodeling, providing valuable information on the pathogenesis of osteoporosis. The role of inflammatory cytokines of the Th1 and Th17 profile in osteoporosis is well known. Here we focus on two newly discovered Th2 cytokines, IL-31 and IL-33, whose implications in osteoporosis are recently emerging. Clinical and experimental observations suggest an important role of the IL-33/IL-31 axis in osteoporosis. IL-33 induces IL-31 secretion by Th2 cells and inhibits RANKL-dependent osteoclastogenesis, thus counteracting bone loss. IL-31 influences Th1/Th17 osteoclastogenetic inflammation and limits Th2 osteoprotective processes, thus favoring osteoporosis. Better knowledge of the role of IL-31 and IL-33 and their receptor complexes in osteoporosis could provide an interesting perspective for the development of new and more effective therapies, possibly with less side effects. Full article
(This article belongs to the Special Issue “IL-33/IL-31 Axis” in Allergic and Immune-Mediated Diseases)
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15 pages, 1119 KiB  
Review
IL-33/IL-31 Axis in Immune-Mediated and Allergic Diseases
by Giuseppe Murdaca, Monica Greco, Alessandro Tonacci, Simone Negrini, Matteo Borro, Francesco Puppo and Sebastiano Gangemi
Int. J. Mol. Sci. 2019, 20(23), 5856; https://doi.org/10.3390/ijms20235856 - 22 Nov 2019
Cited by 96 | Viewed by 6352
Abstract
Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet’s disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to [...] Read more.
Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet’s disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to immunoglobulin (Ig)E production, thus including key cytokines such as interleukin (IL)-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine—it regulates cell proliferation and is involved in tissue remodeling. IL-33, acting through its receptor suppression of tumorigenity (ST2L), is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions. To date, several researchers have investigated the involvement of IL-31 and IL-33 in several allergic and immune-mediated diseases. Further studies are needed to understand the future applications of these molecules as novel therapeutic agents. This paper aims to give the readers a complete and updated review of IL-31 and IL-33 involvement among the most common autoimmune and allergic disorders. Full article
(This article belongs to the Special Issue “IL-33/IL-31 Axis” in Allergic and Immune-Mediated Diseases)
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