The role of innate lymphoid cells in airway inflammation: evolving paradigms

Innate lymphoid cells (ILCs) act as early orchestrators of the immune response, tissue repair, and maintenance of barrier homeostasis. This review summarizes recent findings of the role of ILCs in airway disease and highlights ongoing developments in clinical applications and treatment options. On the basis of the transcription factors required for their development and cytokine profiles, ILCs have been classified into three subsets that resemble those of T-helper subtypes. ILCs produce multiple cytokines in response to signals from activated cells in their local environment. Recent studies in both humans and mice showed that ILCs are located at barrier surfaces and play critical roles in inflammatory diseases of the upper and lower airways. The discovery of ILCs and their characterization in homeostatic and diseased conditions, have brought new insights into innate and adaptive immune responses at mucosal barrier surfaces. The recent progress in understanding the role of ILCs in airway inflammation directs translation of fundamental studies into clinical applications. This knowledge can be useful for future clinical practic

T-cell subsets in the skin and their role in inflammatory skin disorders

T lymphocytes (T-cells) are major players of the adaptive immune response. Naive T-cells are primed in the presence of cytokines, leading to polarization into distinct T-cell subsets with specific functions. These subsets are classified based on their T-cell receptor profile, expression of transcription factors, surface cytokine and chemokine receptors, and their cytokine production, which together determine their specific function. This review provides an overview of the various T-cell subsets and their function in several inflammatory skin disorders ranging from allergic inflammation to skin tumors. Moreover, we highlight similarities of T-cell responses across different skin disorders, demonstrating the presence of similar and opposing functions for the different T-cell subsets. Finally, we discuss the effects of currently available and promising therapeutic approaches to harness T-cells in inflammatory skin diseases for which efficacy next to unwanted side-effects provide new insights into the pathophysiology of skin disorders

Immunoglobulin E autoantibodies in atopic dermatitis associate with Type‐2 comorbidities and the atopic march

Background Autoreactive immunoglobulin E (IgE) antibodies to self-peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well-characterized patients with AD and controls (1.2–88.9 years). Methods Atopic dermatitis patients were sub-grouped in AD with comorbid Type-2 diseases (“AD + Type 2”; asthma, allergic rhinitis, food allergy, n = 431) or “solely AD” (n = 115). Also, subjects without AD but with Type-2 diseases (“atopic controls,” n = 52) and non-atopic “healthy controls” (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples. Results Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD-patients. “AD + Type 2” showed a higher prevalence (16.4%) than “solely AD” (9.6%). “Atopic controls” (9.6%) were comparable with “solely AD” patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with “AD + Type 2”. AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean-section and diversity of domestic pets. Conclusions Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration

Nasal epithelial barrier dysfunction increases sensitization and mast cell degranulation in the absence of allergic inflammation

Background: Increased epithelial permeability has been reported in allergic rhinitis, with histamine and type-2 inflammation being responsible for tight junction dysfunction. The impact of an epithelial barrier defect on allergic sensitization and mast cell (MC) degranulation remains speculative. Methods: Transepithelial passage of allergens was evaluated on primary human nasal epithelial cell cultures. Active sensitization was attempted by repeated intranasal ovalbumin (OVA) applications in Naïve mice. In a passive sensitization model, mice were injected with IgE to Dermatophagoides pteronyssinus (rDer p)2 and then exposed intranasally to the allergen. Chitosan was used to disrupt nasal epithelial integrity in vitro and in vivo. Results: Chitosan strongly reduced transepithelial electrical resistance and facilitated transepithelial allergen passage in cultured primary nasal epithelial cells. In vivo, intranasal chitosan affected occludin expression and facilitated allergen passage. After epithelial barrier disruption, intranasal OVA application induced higher OVA-specific IgG1 and total IgE in serum, and increased eosinophilia and interleukin-5 in bronchoalveolar lavage (BAL) compared to sham-OVA mice. Chitosan exposure, prior to rDer p2 allergen challenge in passively sensitized mice, resulted in increased β-hexosaminidase levels in serum and BAL compared to sham-rDer p2 mice. Intranasal treatment with the synthetic glucocorticoid fluticasone propionate prevented chitosan-induced barrier dysfunction, allergic sensitization, and MC degranulation. Conclusion: Epithelial barrier dysfunction facilitates transepithelial allergen passage, allergic sensitization, and allergen-induced MC degranulation even in the absence of inflammatory environment. These results emphasize the crucial role of an intact epithelial barrier in prevention of allergy