Role of thymic stromal lymphopoietin in allergy and beyond

Barit

The Journal of Dermatology

et al. 2022

Pruritus, also known as itch, is classically defined as an uncomfortable sensation that provokes a desire to scratch. 1 Mild temporal pruritus is non-pathological and physiologically functional to remove external elements from one's own body. On the other hand, severe chronic pruritus is pathological and significantly affects quality of life. 2 Moreover, recurring pruritus leads to repeated scratching (itch-scratch cycle), aggravating disease morbidity by further damaging the skin and increasing proinflammatory cytokine release. 3 Therefore, the treatment of pruritus is important not only for relief from the uncomfortable sensation itself, but also for stopping the itch-scratch cycle, preventing disease exacerbation.Pemphigoid diseases (PDs) are a group of disorders characterized by tense blisters and edematous erythema, which include multiple diseases associated with severe pruritus, such as bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), and linear IgA dermatosis (LAD). 4 Treatment targeting pruritus in PDs is important since itch in PDs is often intractable and significantly impairs patients' quality of life (QOL), with scratch behaviors

Section: Thymic Stromal Lymphopoietinmentioning

confidence: 99%

Section: Mechanisms Of Pruritusmentioning

confidence: 99%

Pruritogens in pemphigoid diseases: Possible therapeutic targets for a burdensome symptom

Barit

The Journal of Dermatology

et al. 2022

“…Evidence suggests that prior DC exposure to these epithelial alarmins, best described with TSLP, causes DCs to influence naïve CD4 + T cells to differentiate into allergen-specific Th2 cells that secrete cytokines IL-5, IL-13, and IL-4. 29 In PBMCs from AR patients, evidence suggests a balance shift from T regulatory cells to Th2 cells compared to healthy control. 30 Activated Th2 cells further interact with cognate allergen-specific B cells which in the presence of IL-4 and possibly IL-13 class switch to IgE.…”

Section: Introductionmentioning

confidence: 99%

B Lineage Cells and IgE in Allergic Rhinitis and CRSwNP and the Role of Omalizumab Treatment

Bai

Tan

2023

Am J Rhinol�Allergy

Background Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two prevalent nasal diseases where both type 2 inflammation and immunoglobulin E (IgE) may play important roles. Although they can exist independently or comorbidly, subtle but important differences exist in immunopathogenesis. Objective To summarize current knowledge of pathophysiological roles of B lineage cells and IgE in AR and CRS with nasal polyps (CRSwNP). Methods Searched PubMed database, reviewed AR and CRSwNP-related literature, and discussed disease diagnosis, comorbidity, epidemiology, pathophysiology, and treatment. Similarities and differences in B-cell biology and IgE are compared in the 2 conditions. Results Both AR and CRSwNP have evidence for pathological type 2 inflammation, B-cell activation and differentiation, and IgE production. However, distinctions exist in the clinical and serological profiles at diagnosis, as well as treatments utilized. B-cell activation in AR may more frequently be regulated in the germinal center of lymphoid follicles, whereas CRSwNP may occur via extrafollicular pathways although controversies remain in these initial activating events. Oligoclonal and antigen-specific IgE maybe predominate in AR, but polyclonal and antigen-nonspecific IgE may predominate in CRSwNP. Omalizumab has been shown efficacious in treating both AR and CRSwNP in multiple clinical trials but is the only Food and Drug Administration-approved anti-IgE biologic to treat CRSwNP or allergic asthma. Staphylococcus aureus frequently colonizes the nasal airway and has the ability to activate type two responses including B-cell responses although the extent to which it modulates AR and CRSwNP disease severity is being investigated. Conclusion This review highlights current knowledge of the roles of B cells and IgE in the pathogenesis of AR and CRSwNP and a small comparison between the 2 diseases. More systemic studies should be done to elevate the understanding of these diseases and their treatment.

“…Studies using airway specimens derived from adults with asthma have confirmed that type 2 pro-asthmatic cytokines, such as Thymic Stromal Lymphopoietin (TSLP), are key mediators in the pathogenesis of the disease ( 4 ). TSLP is a primarily epithelial-derived cytokine released in response to environmental stimuli such as respiratory viruses and allergens ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

TSLP bronchoalveolar lavage levels at baseline are linked to clinical disease severity and reduced lung function in children with asthma

et al. 2022

RationaleThymic stromal lymphopoietin (TSLP) is increasingly recognized as a key molecule in asthma pathogenesis and as a promising therapeutic target in adults. In contrast, in asthmatic children the clinical relevance of TSLP secretion in the lower airways has been remarkably understudied. We tested the hypothesis that pulmonary TSLP levels in asthmatic children correlate with clinical severity, airway inflammation and lower airway obstruction.MethodsBronchoalveolar lavage (BAL) samples and relevant clinical data were collected from asthmatic children undergoing clinically indicated bronchoscopy at Children's National Hospital in Washington D.C. Protein levels of TSLP, IL-5, IL-1β, and IL-33 were quantified in BAL at baseline and correlated with individual severity and clinical features including spirometry, serum IgE and eosinophils, BAL neutrophil and eosinophil counts.ResultsWe enrolled a total of 35 asthmatic children (median age: 9 years). Pediatric subjects with severe asthma had greater TSLP BAL levels at baseline relative to mild or moderate asthmatic subjects (p = 0.016). Asthmatic children with the highest TSLP levels (>75th percentile) had higher IL-5 and IL-1β BAL levels and greater lower airway obstruction (lower FEV1/FVC ratios).ConclusionOur study demonstrates for the first time that higher pulmonary TSLP levels obtained at baseline are linked to asthma disease severity in a subset of children. These data indicate that TSLP may play a key role in the pathogenesis of pediatric asthma and thus provide initial support to investigate the potential use of anti-TSLP biologics to treat severe uncontrolled asthmatic children.