Periostin in Allergy and Inflammation

Matricellular proteins are involved in the crosstalk between cells and their environment and thus play an important role in allergic and inflammatory reactions. Periostin, a matricellular protein, has several documented and multi-faceted roles in health and disease. It is differentially expressed, usually upregulated, in allergic conditions, a variety of inflammatory diseases as well as in cancer and contributes to the development and progression of these diseases. Periostin has also been shown to influence tissue remodelling, fibrosis, regeneration and repair. In allergic reactions periostin is involved in type 2 immunity and can be induced by IL-4 and IL-13 in bronchial cells. A variety of different allergic diseases, among them bronchial asthma and atopic dermatitis (AD), have been shown to be connected to periostin expression. Periostin is commonly expressed in fibroblasts and acts on epithelial cells as well as fibroblasts involving integrin and NF-κB signalling. Also direct signalling between periostin and immune cells has been reported. The deposition of periostin in inflamed, often fibrotic, tissues is further fuelling the inflammatory process. There is increasing evidence that periostin is also expressed by epithelial cells in several of the above-mentioned conditions as well as in cancer. Augmented periostin expression has also been associated with chronic inflammation such as in inflammatory bowel disease (IBD). Periostin can be expressed in a variety of different isoforms, whose functions have not been elucidated yet. This review will discuss potential functions of periostin and its different isoforms in allergy and inflammation.

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Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21207693 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7693

Author(s):

Dhanush Haspula ◽

Michelle A. Clark

Keyword(s):

Cannabinoid Receptors ◽

Cannabinoid Receptor ◽

Inflammatory Diseases ◽

Endocannabinoid System ◽

Future Directions ◽

The Past ◽

Health And Disease ◽

Made In

The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

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Interleukin 17 family members in health and disease

International Immunology ◽

10.1093/intimm/dxab075 ◽

2021 ◽

Author(s):

Soo-Hyun Chung ◽

Xiao-Qi Ye ◽

Yoichiro Iwakura

Keyword(s):

Defense Mechanisms ◽

Helminth Infection ◽

Inflammatory Diseases ◽

Family Members ◽

Interleukin 17 ◽

T Helper ◽

Cytokines And Chemokines ◽

Animal Disease Models ◽

Health And Disease ◽

Inflammatory Bowel

Abstract The interleukin-17 (IL-17) family consists of six family members (IL-17A–IL-17F) and all the corresponding receptors have been identified recently. This family is mainly involved in the host defense mechanisms against bacteria, fungi and helminth infection by inducing cytokines and chemokines, recruiting neutrophils, inducing anti-microbial proteins and modifying T-helper cell differentiation. IL-17A and some other family cytokines are also involved in the development of psoriasis, psoriatic arthritis and ankylosing spondylitis by inducing inflammatory cytokines and chemokines, and antibodies against IL-17A as well as the receptor IL-17RA are being successfully used for the treatment of these diseases. Involvement in the development of inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and tumors has also been suggested in animal disease models. In this review, we will briefly review the mechanisms by which IL-17 cytokines are involved in the development of these diseases and discuss possible treatment of inflammatory diseases by targeting IL-17 family members.

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Epigenetic regulation of epithelial dectin-1 through an IL-33-STAT3 axis in allergic disease

10.1101/2020.11.01.364067 ◽

2020 ◽

Author(s):

Hwan Mee Yong ◽

Naina Gour ◽

Deepika Sharma ◽

Syed Muaz Khalil ◽

Andrew P. Lane ◽

...

Keyword(s):

Epithelial Cells ◽

Allergic Disease ◽

Epigenetic Regulation ◽

Allergic Diseases ◽

Respiratory Epithelium ◽

Fine Tuning ◽

Proximal Promoter ◽

Epigenetic Repression ◽

Inflammatory Molecules

AbstractAllergic diseases arise in susceptible individuals in part because of decrements in protective pathways. The mechanism by which these anti-inflammatory molecules become repressed remains unclear. We have previously reported that epithelial dectin-1 prevents aberrant type 2 responses and is downregulated in the epithelium of allergic patients. Here we report that dectin-1 is constitutively expressed by the respiratory epithelium in humans, and that IL-33 specifically acts as a repressor of dectin-1. Mechanistically, this occurs via IL-33-dependent STAT3 activation and the subsequent repression of the dectin-1 gene, CLEC7A. We have identified a novel enhancer region upstream of the proximal promoter of CLEC7A that is only accessible in epithelial cells, but not in hematopoietic cells. Epigenetic repression of CLEC7A through this newly identified locus, downstream of an aberrant IL-33-STAT3 axis, occurs in the epithelium of allergic individuals. Collectively, our data identify a mechanism of epigenetic fine-tuning of dectin-1 expression in epithelial cells that may participate in allergenicity.

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Contrasting roles of SPARC-related granuloma in bacterial containment and in the induction of anti–Salmonella typhimurium immunity

Journal of Experimental Medicine ◽

10.1084/jem.20071734 ◽

2008 ◽

Vol 205 (3) ◽

pp. 657-667 ◽

Cited By ~ 18

Author(s):

Gianluca Rotta ◽

Gianluca Matteoli ◽

Elisa Mazzini ◽

Paolo Nuciforo ◽

Mario P. Colombo ◽

...

Keyword(s):

Immune Response ◽

Salmonella Typhimurium ◽

Adaptive Immune Response ◽

Matricellular Protein ◽

Matricellular Proteins ◽

Inflammatory Reactions ◽

Adaptive Immune ◽

Draining Lymph Nodes ◽

Increased Susceptibility

The role of matricellular proteins in bacterial containment and in the induction of pathogen-specific adaptive immune responses is unknown. We studied the function of the matricellular protein secreted protein, acidic and rich in cysteine (SPARC/osteonectin) in the dissemination of locally injected Salmonella typhimurium and in the subsequent immune response. We show that SPARC was required for the development of organized acute inflammatory reactions with granuloma-like (GL) features and for the control of bacterial spreading to draining lymph nodes (DLNs). However, SPARC-related GL also inhibited dendritic cell (DC) migration to the DLNs and limited the development of adaptive immune response, thus conferring increased susceptibility to the pathogen. In SPARC-deficient mice, both DC migration and antigen-specific responses were restored against bacteria, leading to protective anti–S. typhimurium immunity. This highlights a new function of matricellular proteins in bacterial infection and suggests that initial containment of bacteria can have drawbacks.

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Glucocorticoid dose-dependent risk of type 2 diabetes in six immune-mediated inflammatory diseases: a population-based cohort analysis

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001220 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001220

Author(s):

Jianhua Wu ◽

Sarah L Mackie ◽

Mar Pujades-Rodriguez

Keyword(s):

Rheumatoid Arthritis ◽

Type 2 Diabetes ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Inflammatory Diseases ◽

Population Based ◽

Immune Mediated ◽

Inflammatory Bowel ◽

Dose Dependent

IntroductionIn immune-mediated inflammatory diseases, there is a lack of -estimates of glucocorticoid dose–response diabetes risk that consider changes in prescribed dose over time and disease activity.Research design and methodsPopulation-based longitudinal analysis of electronic health records from the UK Clinical Practice Research Datalink, linked to hospital admissions and the mortality registry (1998–2017). We included 100 722 adult patients without diabetes history, diagnosed with giant cell arteritis or polymyalgia rheumatica (n=32 593), inflammatory bowel disease (n=29 272), rheumatoid arthritis (n=28 365), vasculitis (n=6082), or systemic lupus erythematosus (n=4410). We estimated risks and HRs of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods.ResultsAverage patient age was 58.6 years, 65 469 (65.0%) were women and 8858 (22.6%) had a body mass index (BMI) ≥30 kg/m2. Overall, 8137 (8.1%) people developed type 2 diabetes after a median follow-up of 4.9 years. At 1 year, the cumulative risk of diabetes increased from 0.9% during periods of non-use to 5.0% when the daily prednisolone-equivalent dose was ≥25.0 mg. We found strong dose-dependent associations for all immune-mediated diseases, BMI levels and underlying disease duration, even after controlling for periods of active systemic inflammation. Adjusted HR for a <5.0 mg daily dose versus non-use was 1.90, 95% CI 1.44 to 2.50; range 1.70 for rheumatoid arthritis to 2.93 for inflammatory bowel disease.ConclusionsWe report dose-dependent risks of type 2 diabetes associated with glucocorticoid use for six common immune-mediated inflammatory diseases. These results underline the need for regular diabetic risk assessment and testing during glucocorticoid therapy in these patients.

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Specific detection of cell-free DNA derived from intestinal epithelial cells using methylation patterns

10.1101/409219 ◽

2018 ◽

Cited By ~ 2

Author(s):

Roni Lehmann-Werman ◽

Aviad Zick ◽

Cloud Paweletz ◽

Marisa Welch ◽

Ayala Hubert ◽

...

Keyword(s):

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Ductal Adenocarcinoma ◽

Intestinal Epithelial ◽

Specific Detection ◽

Cell Free Dna ◽

Free Dna ◽

Health And Disease ◽

Inflammatory Bowel ◽

Methylation Patterns

AbstractEpithelial cells of the intestine undergo rapid turnover and are thought to be cleared via stool. Disruption of tissue architecture, as occurs in colorectal cancer (CRC), results in the release of material from dying intestinal epithelial cells to blood. This phenomenon could be utilized for diagnosis and monitoring of intestinal diseases, if circulating cell-free DNA (cfDNA) derived from intestinal cells could be specifically identified. Here we describe two genomic loci that are unmethylated specifically in intestinal epithelial cells, allowing for sensitive and specific detection of DNA derived from such cells. As expected, intestinal DNA is found in stool, but not in plasma, of healthy individuals. Patients with inflammatory bowel disease (IBD) have minimal amounts of intestinal cfDNA in the plasma, whereas patients with advanced CRC show a strong signal. The intestinal markers are not elevated in plasma samples from patients with pancreatic ductal adenocarcinoma (PDAC), and a combination of intestine- and pancreas-specific markers allowed for robust differentiation between plasma cfDNA derived from CRC and PDAC patients. Intestinal DNA markers provide a mutation-independent tool for monitoring intestinal dynamics in health and disease.

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IL-36 cytokines in inflammatory and malignant diseases: not the new kid on the block anymore

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03909-4 ◽

2021 ◽

Author(s):

James Byrne ◽

Kevin Baker ◽

Aileen Houston ◽

Elizabeth Brint

Keyword(s):

Wound Healing ◽

Sequence Homology ◽

Inflammatory Bowel Diseases ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Malignant Diseases ◽

Bowel Diseases ◽

Health And Disease ◽

Inflammatory Bowel

AbstractThe IL-36 family of cytokines were first identified in 2000 based on their sequence homology to IL-1 cytokines. Over subsequent years, the ability of these cytokines to either agonise or antagonise an IL-1R homologue, now known as the IL-36 Receptor (IL-36R), was identified and these cytokines went through several cycles of renaming with the current nomenclature being proposed in 2010. Despite being identified over 20 years ago, it is only during the last decade that the function of these cytokines in health and disease has really begun to be appreciated, with both homeostatic functions in wound healing and response to infection, as well as pathological functions now ascribed. In the disease context, over activation of IL-36 has now been associated with many inflammatory diseases including Psoriasis and inflammatory bowel diseases, with roles in cancer also now being investigated. This review summarises the current knowledge of IL-36 biology, its role in inflammatory diseases and focuses on an emerging role for IL-36 in cancer.

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Immunoregulatory T cell epitope peptides for the treatment of allergic disease

Immunotherapy ◽

10.2217/imt-2021-0133 ◽

2021 ◽

Vol 13 (15) ◽

pp. 1283-1291

Author(s):

Rashi Ramchandani ◽

Lubnaa Hossenbaccus ◽

Anne K Ellis

Keyword(s):

Allergic Rhinitis ◽

T Cell ◽

Treatment Algorithm ◽

Cell Epitope ◽

Japanese Cedar ◽

Allergic Diseases ◽

T Cell Epitope ◽

Inflammatory Reactions ◽

Cedar Pollen

Allergic diseases are type 2 inflammatory reactions with an increasing worldwide prevalence, making the search for new therapeutic options pertinent. Allergen immunotherapy is the only disease-modifying approach for allergic rhinitis, though it can result in systemic reactions. Recently, peptide immunotherapy (PIT), involving T-cell epitope peptides that bind to major histocompatibility complexes, have been developed. It is speculated that they can induce T helper cell type 2 anergy, Treg cell upregulation or immune deviation. Promising results in cat dander, honeybee venom, Japanese cedar pollen, grass pollens, ragweed and house dust mite clinical trials have shown safety, efficacy and tolerability to PIT. Hence, PIT may hold the potential to change the treatment algorithm for allergic rhinitis.

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Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease

Physiological Reviews ◽

10.1152/physrev.00054.2017 ◽

2018 ◽

Vol 98 (4) ◽

pp. 1983-2023 ◽

Cited By ~ 57

Author(s):

Peter Hegyi ◽

Jozsef Maléth ◽

Julian R. Walters ◽

Alan F. Hofmann ◽

Stephen J. Keely

Keyword(s):

Epithelial Cells ◽

Bile Acids ◽

Epithelial Transport ◽

Enterohepatic Circulation ◽

Chronic Diarrhea ◽

The Body ◽

Intestinal Epithelial ◽

Health And Disease ◽

Specific Receptors ◽

Inflammatory Bowel

Epithelial cells line the entire surface of the gastrointestinal tract and its accessory organs where they primarily function in transporting digestive enzymes, nutrients, electrolytes, and fluid to and from the luminal contents. At the same time, epithelial cells are responsible for forming a physical and biochemical barrier that prevents the entry into the body of harmful agents, such as bacteria and their toxins. Dysregulation of epithelial transport and barrier function is associated with the pathogenesis of a number of conditions throughout the intestine, such as inflammatory bowel disease, chronic diarrhea, pancreatitis, reflux esophagitis, and cancer. Driven by discovery of specific receptors on intestinal epithelial cells, new insights into mechanisms that control their synthesis and enterohepatic circulation, and a growing appreciation of their roles as bioactive bacterial metabolites, bile acids are currently receiving a great deal of interest as critical regulators of epithelial function in health and disease. This review aims to summarize recent advances in this field and to highlight how bile acids are now emerging as exciting new targets for disease intervention.

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