CRTH2 antagonists in the treatment of allergic responses involving TH2 cells, basophils, and eosinophils

Townley, Robert G.; Agrawal, Swati

doi:10.1016/j.anai.2012.04.004

Cited by 28 publications

(20 citation statements)

References 50 publications

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“…188 Neutralization of the IL-33/ST2 pathway in asthmatic patients might be predicted to have similar benefit, and its translation to patients is underway. 189 Also being explored are CRTH2 antagonists 190 and CRTH2 depleting mAbs, 191 which target memory T H 2 cells, as well as CRTH2 + innate immune cells (eosinophils, basophils, and ILC2s) that have homed to the lungs.…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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“…Other leukocytes including Th2 cells 20 and dendritic cells (DCs) 21 produce PGD 2 at lower levels. PGD 2 signals through receptors DP 1 and DP 2 (also known as CRTH2 or chemoattractant homologous molecule expressed on Th2 cells ) 22 . Aerosolized PGD 2 administered to sensitized mice prior to antigen challenge increases the numbers of eosinophils and the levels of Th2 cytokines found in BAL fluid 23 .…”

Section: Selected Prostanoidsmentioning

confidence: 99%

Lipid mediators and allergic diseases

Fanning

Boyce

2013

Annals of Allergy, Asthma & Immunology

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“…When exposed to an allergen challenge, the production of prostaglandin D 2 increases, and when binding to CRTH2 it facilitates the activation and a positive feedback loop in chemotaxis of Th2 cells, eosinophils, and to lesser extent basophils [91]. CRTH2 signalling is thought to be involved in the activation of allergological pathways and Th2 immune activation [92]; thus, the development of small molecules targeting the CRTH2 could be beneficial to AD patients as a means of correcting a skewed Th2 response and reducing eosinophil activity.…”

Section: Chemoattractant Receptor Homologues Molecule Expressed On Thmentioning

confidence: 99%

Emerging Treatment Options in Atopic Dermatitis: Systemic Therapies

Nygaard

Vestergaard

Deleuran³

2017

Dermatology

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The pathogenesis of atopic dermatitis (AD) is multifactorial and intricate, and the clinical presentation of the condition varies greatly. Symptoms and severity depend on individual trigger factors and stage of the disease. The majority of AD patients are sufficiently treated with emollients in combination with existing topical or systemic therapies. Yet treatment failure with existing drugs and treatment options can be a significant clinical problem. New treatments are under development, and the majority of these new drugs focus on targeting a skewed immune response in AD. Novel therapeutic approaches, which target the pathways involved in the pathogenesis of AD, may provide a potentially more effective and less harmful approach to systemic therapy. These pharmaceutical agents are designed to narrowly modify or directly block a specific cellular signal or pro-inflammatory pathway. We review systemic drugs in the pipeline for AD. To make the review as current and pertinent as possible, we selected to focus on AD-related therapies available in the clinicaltrials.gov database with a first received date after January 1, 2014, up until May 31, 2017. We excluded therapies that could be categorized as either traditional Chinese medicine, herbal medicine, probiotics, histamine/leukotriene blockers, immuno-adsorption, or immunostimulants.

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CRTH2 antagonists in the treatment of allergic responses involving TH2 cells, basophils, and eosinophils

Cited by 28 publications

References 50 publications

Pathogenic CD4 + T cells in patients with asthma

Pathogenic CD4 + T cells in patients with asthma

Lipid mediators and allergic diseases

Emerging Treatment Options in Atopic Dermatitis: Systemic Therapies

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