Allergen‐induced interleukin‐18 promotes experimental eosinophilic oesophagitis in mice

Dutt, Parmesh; Shukla, Jai Shankar; Ventateshaiah, Sathisha Upparahalli; Mariswamy, Siddesha Jalahalli; Mattner, Jochen; Shukla, Anshi; Mishra, Anil

doi:10.1038/icb.2015.84

Cited by 7 publications

(14 citation statements)

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“…In recent years, there has been major progress in understanding the involvement of eosinophil and mast cell accumulation esophageal remodeling and functional esophageal abnormalities; however, the mode of EoE induction, its progression, diagnosis and it management are currently not well proven [11,13,58,59,83–85]. EoE was first described in 1978 and clinically recognized in 1994 further it was well accepted with distinct characteristics and nomenclature in 2007, and was recently updated in 2011 [86–89].…”

Section: Eosinophilic Esophagitismentioning

confidence: 99%

“…But, there are limitations that exist with oral swallowed steroids therapy: dependency on treatment (reoccurrence of EoE symptoms within few months after discontinuation of therapy). Our, most recent report indicates that IL-18 and iNKT cells are induced in EoE patients and IL-18 activate iNKT cells; therefore neutralization of iNKT cells, IL-18 or IL8Rα may be a possible therapeutic target for EoE [124,125]. Taken together, much progress has been made concerning the EGID therapy, but there is still lack of mechanistic understanding compared with other cell types and gastrointestinal diseases like IBD.…”

Section: Treatment Strategies Of Egidmentioning

confidence: 99%

“…These lipid mediators increase vascular permeability and mucous secretion, and are potent stimulators of smooth muscle contraction [48]. Eosinophil stimulates inflammatory cell recruitment and triggers the secretion of fibrogenic mediators resulting in tissue remodeling, disruption of epithelial integrity by affecting the fibroblasts, smooth muscles, and cell-adhesion molecules [11,13,58–60]. …”

Section: Introductionmentioning

confidence: 99%

“…IL-13 is considered to be more of an effector cytokine in pathogenesis compared to IL-4, as suggested by the finding that a soluble IL-13 receptor blocks many essential qualities of the experimental disease [60,69,70]. Most recently, we showed a critical role of food allergen-induced IL-18 and invariant natural killer T cells in human and experimental gastrointestinal allergic disease [3,13,81]. …”

Section: Introductionmentioning

confidence: 99%

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Elements Involved In Promoting Eosinophilic Gastrointestinal Disorders

Shukla

Mishra

Venkateshaiah

et al. 2015

J Genet Syndr Gene Ther

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Eosinophilic gastrointestinal disorders (EGID) are food allergen-induced allergic gastrointestinal disorders, characterized by accumulation of highly induced eosinophils in different segments of gastrointestinal tract along with eosinophil microabssess and extracellular eosinophilic granules in the epithelial layer. EGID are both IgE- and cell-mediated group of diseases that include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE) and eosinophilic colitis (EC). Despite the increased incidences and considerable progress made in understanding EGID pathogenesis. The mechanism is still not well understood. It has been shown that IL-4, IL-5, IL-13, IL-15, IL-18, eotaxin-1, eotaxin-2 and eotaxin-3 play a critical role in EGID pathogenesis. Currently, the only criterion for diagnosing EoE, EGE and EC are repetitive endoscopic and histopathological evaluation of biopsies along with other clinical characteristics/manifestations. Antigen elimination and corticosteroid therapies are the most effective therapies currently in practice for the treatment of EGID. The cytokines (anti-IL-5 and anti-IL-13) therapy trials were not very successful in case of EoE. Most recently, a clinical trial using anti-IL-13 reported only 60% reduced esophageal eosinophilia without achieving primary endpoint. This clinical finding is not surprising and is in accordance with our earlier report indicating that IL-13 is not critical in the initiation of EoE. Notably, EGID still has no reliable noninvasive diagnostic biomarkers. Hence, there is a great necessity to identify novel noninvasive diagnostic biomarkers that can easily diagnose EGID and provide an effective therapy. Now, the attention is required to target cell types like iNKT cells that produce eosinophil active cytokines and is found induced in the pathogenesis of both experimental and human EoE. iNKT cell neutralization is shown to protect allergen-induced EoE in experimental model. In this review, we have discussed the key elements that are critical in the disease initiation, progression, pathogenesis and important for future diagnostic and therapeutic interventions for EGID.

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Section: Eosinophilic Esophagitismentioning

confidence: 99%

Section: Treatment Strategies Of Egidmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Elements Involved In Promoting Eosinophilic Gastrointestinal Disorders

Shukla

Mishra

Venkateshaiah

et al. 2015

J Genet Syndr Gene Ther

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“…Interestingly, it has been suggested that milk lipids could also be the driving force in another iNKT cell dependent allergic inflammation (Jyonouchi et al 2014). Eosinophilic esophagitis (EoE) is a chronic allergic inflammation of the esophagus (Wechsler and Bryce 2014), and mouse models demonstrated that iNKT cells and their Th2 cytokines are required for the disease (Dutt et al 2015;Rajavelu et al 2012;Rayapudi et al 2014). In EoE patients, iNKT cell numbers and Th2 cytokines are increased in the esophagus (Jyonouchi et al 2014;Lexmond et al 2014;Rayapudi et al 2014) and normalize following dietary removal of the allergen (Lexmond et al 2014).…”

Section: Further Aspects Of Environmental Inkt Cell Antigensmentioning

confidence: 99%

From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells

Wingender

2015

Arch. Immunol. Ther. Exp.

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Invariant natural killer T (iNKT) cells are a unique subset of innate T cells that share features with innate NK cells and adaptive memory T cells. The first iNKT cell antigen described was found 1993 in a marine sponge and it took over 10 years for other, bacterial antigens to be described. Given the paucity of known bacterial iNKT cell antigens, it appeared as if iNKT cells play a very specialist role in the protection against few, rare and unusual pathogenic bacteria. However, in the last few years several publications painted a very different picture, suggesting that antigens for iNKT cells are found almost ubiquitous in the environment. These environmental iNKT cell antigens can shape the distribution, phenotype and function of iNKT cells. Here, these recent findings will be reviewed and their implications for the field will be outlined.

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Microbiome and its impact on gastrointestinal atopy

Muir

Benitez

Dods

et al. 2016

Allergy

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The prevalence of allergic conditions has continuously increased in the last few decades in Westernized countries. A dysbiotic gut microbiome may play an important role in the development of allergic diseases. Genetic, environmental and dietary factors may alter the commensal microbiota leading to inflammatory dysregulation of homeostasis. Murine and human studies have begun to elucidate the role of the microbiota in the pathogenesis of atopic diseases including asthma, atopic dermatitis and food allergies. However, the role of the microbiome in most eosinophilic gastrointestinal diseases (EGIDs) is not yet known. This review provides an overview of what is currently known about the development of tolerance from both molecular and clinical standpoints. We also look at the gut specific microbiome and its role in atopic conditions with the hope of applying this knowledge to the understanding, prevention and treatment of EGIDs, particularly EoE.

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Allergen‐induced interleukin‐18 promotes experimental eosinophilic oesophagitis in mice

Cited by 7 publications

References 0 publications

Elements Involved In Promoting Eosinophilic Gastrointestinal Disorders

Elements Involved In Promoting Eosinophilic Gastrointestinal Disorders

From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells

Microbiome and its impact on gastrointestinal atopy

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