Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis

Mack, Madison R.; Brestoff, Jonathan R.; Berrien-Elliott, Melissa M.; Trier, Anna M.; Yang, Ting; McCullen, Matthew; Collins, Patrick L.; Niu, Haixia; Bodet, Nancy D.; Wagner, Julia A.; Park, Eugene; Xu, An; Wang, Fang; Chibnall, Rebecca; Heffington, Carrie; Kreisel, Friederike; Margolis, David J.; Sheinbein, David; Lovato, Paola; Vivier, Éric; Cella, Marina; Colonna, Marco; Yokoyama, Wayne M.; Oltz, Eugene M.; Fehniger, Todd A.; Kim, Brian

doi:10.1126/scitranslmed.aay1005

Cited by 60 publications

(88 citation statements)

References 78 publications

(96 reference statements)

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“…NK cells deficiencies are distinguished in patients with AD and NK cells limit ILC2 inflammation in the skin in a murine model of AD induced by MC903. Moreover, NK cell‐boosting IL‐15 superagonist clearly shows the beneficial effect in this murine model 170 . NKT cell, NK cell, and IFN‐γ may play an essential role in the immunoregulation in the type 2 inflammation of lung and skin.…”

Section: Other Cells That Contribute To Type 2 Immunitymentioning

confidence: 63%

Type 2 immunity in the skin and lungs

Akdiş

Arkwright

Brüggen

et al. 2020

Allergy

323

287

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There has been extensive progress in understanding the cellular and molecular mechanisms of inflammation and immune regulation in allergic diseases of the skin and lungs during the last few years. Asthma and atopic dermatitis (AD) are typical diseases of type 2 immune responses. interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin are essential cytokines of epithelial cells that are activated by allergens, pollutants, viruses, bacteria, and toxins that derive type 2 responses. Th2 cells and innate lymphoid cells (ILC) produce and secrete type 2 cytokines such as IL-4, IL-5, IL-9, and IL-13. IL-4 and IL-13 activate B cells to class-switch to IgE and also play a role in T-cell and eosinophil migration to allergic inflammatory tissues. IL-13 contributes to maturation, activation, nitric oxide production and differentiation of epithelia, production of mucus as well as smooth muscle contraction, and extracellular matrix generation. IL-4 and IL-13 open tight junction barrier and cause barrier leakiness in the skin and lungs. IL-5 acts on activation, recruitment, and survival of eosinophils. IL-9 contributes to general allergic phenotype by enhancing all of the aspects, such as IgE and eosinophilia. Type 2 ILC contribute to inflammation in AD and asthma by enhancing the activity of Th2 cells, eosinophils, and their cytokines. Currently, five biologics are licensed to suppress type 2 inflammation via IgE, IL-5 and | 1583 AKDIS et Al. 1 | INTRODUC TI ON Allergic diseases cause significant morbidity and mortality with almost one billion cases, accounting for a significant portion of overall healthcare costs. The dysregulated immune response, chronic inflammation, and remodeling in the affected tissues define a dynamic and heterogeneous spectrum of anaphylaxis, food allergy, asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyposis (CRSwNP), and atopic dermatitis (AD). Two main subtypes of immune responses driving asthma and AD have been defined, namely type 2-high and type 2-low. 1-4 Precision medicine and biomarker discovery is important for the management of asthma and AD in the context of a better selection of good responders to treatment, prediction of outcomes, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven diseases. In contrast, the non-type 2 immune response in asthma and AD is insufficiently understood. The majority of patients with AD, CRS and asthma involve, or result from, an overexpression of type 2 inflammatory pathways (Figure 1). 5-7 A specific type 2 set of cytokines are produced during the induction and maintenance of allergic immune response with the contribution of epithelial cells, dendritic cells (DC), T cells, innate lymphoid cells (ILC), eosinophils, mast cells (MC), and basophils. Activation of Th2 and ILC2 pathways is at the core of type 2 inflammation. Th2 cytokines include interleukin (IL)-4, IL-5, IL-9, IL-13, and IL-31, and main type 2 cytokines of ILC2 are IL-5, IL-9, and IL-13. 8,9 IL-4 induces Th2 cell di...

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Section: Other Cells That Contribute To Type 2 Immunitymentioning

confidence: 63%

Type 2 immunity in the skin and lungs

Akdiş

Arkwright

Brüggen

et al. 2020

Allergy

323

287

View full text Add to dashboard Cite

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“… 16 Natural killer cells have recently been found to be deficient in patients with AD. 17 This deficiency may also contribute to increased type 2 inflammation owing to a potential counter-regulatory mechanism between the natural killer cells and type 2 inflammation. 17 …”

Section: What Causes An Increase In Infections In Ad?mentioning

confidence: 99%

The infectious complications of atopic dermatitis

Wang

Boguniewicz

et al. 2021

Annals of Allergy, Asthma & Immunology

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Objective Atopic dermatitis (AD) is a chronic inflammatory skin disease that is complicated by an increased risk for skin and systemic infections. Preventive therapy for AD is based on skin barrier improvement and anti-inflammatory treatments, whereas overt skin and systemic infections require antibiotics or antiviral treatments. This review updates the pathophysiology, diagnosis, management, controversy of antibiotic use, and potential treatments of infectious complications of AD. Data Sources Published literature obtained through PubMed database searches and clinical pictures. Study Selections Studies relevant to the mechanisms, diagnosis, management, and potential therapy of infectious complications of AD. Results Skin barrier defects, type 2 inflammation, Staphylococcus aureus colonization, and cutaneous dysbiosis are the major predisposing factors for the increased infections in AD. Although overt infections require antibiotics, the use of antibiotics in AD exacerbation remains controversial. Conclusion Infectious complications are a comorbidity of AD. Although not common, systemic bacterial infections and eczema herpeticum can be life-threatening. Preventive therapy of infections in AD emphasizes skin barrier improvement and anti-inflammatory therapy. The use of antibiotics in AD exacerbation requires further studies.

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“…A few studies reported quantitative and qualitative alterations in NK cells in peripheral blood, in particular reduced relative proportions of peripheral blood NK cells and a reduced cytotoxicity in AD. [7][8][9][10][11] Furthermore, NK cells were detected in dermal infiltrates of AD lesional skin (LS), whereas in nonlesional skin (NLS) and HS only few or no NK cells were detected. 2 More recently, a selective reduction of mature CD56 dim CD57 1 NK cells in peripheral blood, which was largely reverted by treatment with the anti-IL-4Ra antibody dupilumab, as well as an enrichment of activated NK-cell transcriptomic signatures in LS was reported in a small cohort of adults with moderate to severe AD.…”

Section: Introductionmentioning

confidence: 99%