Asthma, Allergic Clinical Trial
Official title:
Lung-Resident Memory Th2 Cells in Asthma
Determining how memory T helper type 2 (Th2) initiate recall responses to aeroallergens has the potential to change the therapeutic approach to allergic asthma, the most common asthma subtype. ~5-10% of effector Th2 cells recruited into the lung give rise to long-lived tissue resident memory cells that are poised to respond upon allergen re-exposure.Consequently, targeting memory Th2 cell activation is an attractive therapeutic strategy. However, it is not well understood how allergen inhalation initiates a memory Th2 cell response in the lung. The focus of this new study on the role of lung-resident memory Th2 cells in orchestrating the recall response to allergen in the lung, including the recruitment and activation of circulating Th2 cells, is a natural, timely and exciting extension of the investigators' ongoing Allergen Challenge Protocol.
The objective of this study is to define the mechanisms whereby Th2-Trm persisting in the lung orchestrates a recall response to inhaled allergens. The investigators' central hypothesis is that Th2-Trm ignite allergic airway inflammation via a rapid and enhanced response to cognate antigen in the airway and the ability to recruit circulating Th2 cells (Th2-Tcr) to the sites of antigen presentation in the lung. Mechanistically, the investigators hypothesize that Th2-Trm co-localize with DCs expressing the Th2 cell-attracting chemokine CCL17 and after allergen re-challenge rapidly produce type 2 cytokines that initiate allergic inflammation and markedly enhance DC expression of CCL17. This increased CCL17 expression recruits Th2-Tcr cells from the blood to sites of antigen presentation where Th2-Tcr receive a "second touch" from cognate antigen loaded and activated DCs and become fully competent to amplify allergic inflammation. The investigators propose to use innovative experimental systems to define the function of Th2-Trm, including single cell RNA-seq analysis of human airway mucosal CD4+ T cells obtained via bronchial brushing. Specifically, the investigators propose to define the transcriptional phenotype of human lung Th2-Trm and Th2-Tcr. Defining the mechanisms regulating Th2-Trm function in the asthmatic airway has the potential to yield new therapeutic approaches for allergic asthma. Memory CD4+ T helper type 2 (Th2) cells are critical in promoting allergic asthma, the most common asthma endotype. The investigators propose to define the function of newly described lung-resident memory Th2 cells in driving recurrent allergic airway inflammation. The successful completion of the proposed study has the potential to focus new asthma therapies on specifically targeting the biology of lung-resident memory Th2 cells. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04435990 -
Efficacy and Safety Evaluation for the Treatment of Allergy Against Mites
|
Phase 3 | |
Completed |
NCT03563521 -
Identifying Serum Cytokine Profiles of Distinct Inflammatory Phenotypes in Severe Asthma
|
||
Completed |
NCT02990117 -
ICS Treatment Compliance of Asthma Patients
|
||
Completed |
NCT03468790 -
Anti-IgE Monoclonal Antibody Treatment in Patients With Allergic Asthma.
|
Phase 3 | |
Recruiting |
NCT04898283 -
Efficacy and Safety Evaluation of the Treatment of Allergy Against Cupressaceae and Grasses.
|
Phase 3 | |
Not yet recruiting |
NCT05352126 -
Effects of Puressentiel Purifying Spray on Asthma Control in Patients With Mild to Moderate Allergy-induced Asthma.
|
N/A | |
Completed |
NCT01104012 -
Validation of Proteomic Analyses for Allergic Asthma and Rhinitis
|
N/A | |
Not yet recruiting |
NCT06027073 -
Biologics and Sublingual Immunotherapy
|
Phase 4 | |
Recruiting |
NCT05720325 -
Dupilumab Effects Against Aeroallergen Challenge
|
Phase 2 | |
Completed |
NCT03112577 -
Study of REGN3500 and Dupilumab in Patients With Asthma
|
Phase 1 | |
Recruiting |
NCT04891237 -
Efficacy and Safety Evaluation for the Treatment of Allergy Against Grass and Olive Pollen
|
Phase 3 | |
Terminated |
NCT02953106 -
Effects of Intranasal Fluticasone Plus Azelastine on Airway Inflammation in Patients With Asthma & Allergic Rhinitis
|
Phase 4 | |
Completed |
NCT06063044 -
Food-specific IgG4-guided Elimination Diets Improve Allergy Symptoms in Children
|
||
Completed |
NCT03705325 -
Evaluating Asthma Exacerbation-induced Changes in Lung Function With a Home-based Spirometer
|
N/A | |
Recruiting |
NCT05478824 -
IL13 Signaling in Allergic Asthma
|
||
Suspended |
NCT04109807 -
Effects of Low Dose Ozone on Airway Inflammatory Responses in Adults With Asthma - Sedentary Nasal Ozone (Asthma SNOZ)
|
N/A | |
Withdrawn |
NCT04035109 -
Anakinra as a Rescue Treatment for Allergic Inflammation
|
Phase 1/Phase 2 | |
Recruiting |
NCT03983603 -
Plant Stanol Esters and Preventing Asthma Symptoms
|
N/A | |
Not yet recruiting |
NCT05740748 -
Tezepelumab and Methacholine Airway Hyperresponsiveness in Participants With Mild Allergic Asthma
|
Phase 2 |