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• W4241110446 abstract "Early-life viral respiratory tract infections are associated with development of asthma and atopic disease. The mechanisms linking viral infections to postviral atopy are not understood. Using human samples and a mouse model, Cheung et al (p 1206) demonstrated an important role for a subset of neutrophils and leukotrienes in translation of viral respiratory tract infections into postviral atopic disease.•CD49d-expressing neutrophils are increased in nasal lavage fluid of human subjects with symptoms of an upper respiratory tract infection.•There are “pro-atopic” mouse and human CD49d+ neutrophils that express cysteinyl leukotriene receptor type 1 (CysLTR1), a receptor for cysteinyl leukotrienes.•In the mouse, cysteinyl leukotrienes provide a survival signal to CD49d+ neutrophils.•Blockade of CysLTR1 during the first days of a viral respiratory tract infection prevents postviral atopic airway disease in a mouse model. Targeting this “pro-atopic” neutrophil subset, perhaps through leukotriene blockade, might be a useful strategy to prevent development of postviral atopic disease. Low-density lipoprotein receptor–related protein 1 (LRP-1) is a scavenger-type endocytic receptor that binds multiple ligands. In this issue, Mishra et al (p 1066) show that LRP-1 plays an important role in modulating dendritic cell (DC) function during house dust mite (HDM)–induced allergic airway inflammation with the following findings:•Myeloid DCs from the blood of patients with eosinophil-high asthma, as well as CD11b+ DCs from the lungs of HDM-challenged mice, have reduced LRP-1 expression.•Adoptive transfer of HDM-pulsed LRP-1–deficient CD11b+ DCs to naive wild-type mice increased eosinophilic airway inflammation after HDM challenge.•HDM-challenged mice with a specific deletion of LRP-1 in CD11c+ cells, which include DCs and alveolar macrophages, have increased eosinophilic airway inflammation, allergic sensitization, TH2 cytokine production, and mucous metaplasia.•LRP-1–deficient DCs show increased uptake and presentation of HDM antigen. These findings identify LRP-1 as a novel negative regulator of DC-mediated adaptive immunity in HDM-induced eosinophilic airway inflammation and suggest that LRP-1 might modulate the type 2–high asthma endotype in human subjects. The incidence of peanut allergy has been increasing. However, little is known regarding the immunologic mechanism or mechanisms that initiate peanut allergy. TH2-type CD4+ T cells are generally involved in the allergic immune response. In this issue, using mouse models, Dolence et al (p 1144) report that follicular helper T (TFH) cells, rather than conventional TH2 cells, promote peanut allergy, as supported by the following major findings (see Figure):•Inhalation of peanut flour fine particles generated a large number of IL-4–producing TFH cells in lymph nodes.•TFH cells exceeded TH2 cells in their capacity to help B cells produce IgE antibody.•Depletion of TFH cells resulted in a marked decrease in serum levels of peanut-specific IgE and protected mice from anaphylaxis. Overall, TFH cells need to be examined further for their role in patients with allergic diseases, in particular those involving IgE- or antibody-dependent clinical phenotypes. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease. Because AD requires long term treatment, drugs for AD must have a very good safety profile. In this issue, Kabashima et al (p 1121) describe the efficacy and safety of nemolizumab, an anti–IL-31 receptor A humanized mAb in patients with AD. Subcutaneous nemolizumab was given every 4 or 8 weeks to patients with moderate-to-severe AD inadequately controlled by topical agents in an initial 12-week phase II clinical trial (n = 264), followed by up to 64 weeks of extension treatment (n = 191). The main findings were:•Improvement in pruritus and dermatitis scores observed during the initial 12 weeks was maintained or increased throughout the 64-week extension period.•Nemolizumab was well tolerated throughout the 64-week extension period, and no new safety concerns were identified. These results support the potential value of anti–IL-31 therapy in the treatment of moderate-to-severe AD and associated pruritus. Several therapies targeting IL-4, IL-13, or IL-5 have recently become available for the treatment of severe asthma and other allergic diseases. However, only a subset of patients responds favorably to any single agent, indicating that some of the severe asthma clusters might require targeting of more than 1 cytokine in parallel. Godar et al (p 1185) developed an antibody to simultaneously target IL-4, IL-13, and IL-5.•A bispecific antibody was successfully generated to neutralize both IL-4 receptor α and IL-5 with equal potency as the individual monospecific antibodies.•In a preclinical mouse asthma model driven by house dust mite, the bispecific antibody (but none of the individual monospecific antibodies) was able to completely inhibit the features of asthma, such as bronchial hyperreactivity and difficult-to-treat mucus overproduction. This study should give impetus to developing and testing bispecific antibodies to target multiple cytokines for difficult-to-treat allergic diseases in human subjects. Leukotriene E4 (LTE4) is the final active metabolite of the cysteinyl leukotrienes (CysLTs), which are key mediators in asthma pathogenesis. Results from animal studies have suggested the presence of a distinct LTE4 receptor, meaning that current CysLT1 receptor antagonists might provide incomplete inhibition of CysLT responses. In this issue, Lazarinis et al (p 1080) tested this hypothesis by assessing the influence of the CysLT1 antagonist montelukast in responses induced by inhalation of LTE4 in 16 asthmatic patients. Major findings were:•The effect of LTE4 on airway smooth muscle in asthmatic patients is mediated exclusively by the CysLT1 receptor.•Urinary excretion of all major lipid mediators increased after LTE4 inhalation, predominately prostaglandin D2, suggesting that LTE4 can activate mast cells in vivo (see Figure). Montelukast inhibited both the bronchoconstriction and mast cell activation induced by inhalation of LTE4. These new findings suggest that CysLTs might need to be reclassified as both directly and indirectly acting bronchoconstrictors." @default.
• W4241110446 created "2022-05-12" @default.
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• W4241110446 date "2018-10-01" @default.
• W4241110446 modified "2023-09-27" @default.
• W4241110446 title "The Editors' Choice" @default.
• W4241110446 doi "https://doi.org/10.1016/j.jaci.2018.08.019" @default.
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