News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2021)

Verma et al (J Exp Med 2021;218:e20201354; https://doi.org/10.1084/jem.20201354) identified molecular and epigenetic mechanisms underlying immunologic memory of group 2 innate lymphoid cells (ILC2s) in asthma. More specifically, repetitive exposure of Rag1-/- mice, which lack mature B and T lymphocytes, to Alternaria fungal extract allowed weeks later for enhanced asthma-like responses with exposure to a decreased dose that critically depended on lung ILC2s. Extensive genome-wide analyses revealed a distinct epigenetic landscape in memory ILC2s, and immunologic memory required a balance of 2 distinct gene expression programs that mediated gene repression and preparedness. Finally, memory ILC2s were present at increased frequency in sensitized mice and in asthma patients. These results have furthered our understanding of how memory ILC2s may contribute to the pathogenesis of asthma.Rafeul AlamView Large Image Figure ViewerDownload Hi-res image Download (PPT) We asked corresponding author Rafeul Alam, MD, PhD, of the Division of Allergy & Immunology, Department of Medicine, National Jewish Health, and the School of Medicine at the University of Colorado Denver, both located in Denver, Colorado, to comment on the study. He writes, “ILC2 memory could help explain the persistence of type-2 inflammation in chronic asthma and other eosinophilic disorders.”A distinct epigenetic landscape in memory ILC2s A distinct epigenetic landscape in memory ILC2s Antigen presentation is critical to the maintenance of established food allergy, but the underlying immune mechanisms are incompletely understood. Zhou et al (J Exp Med 2021;218:e20201793; https://doi.org/10.1084/jem.20201793) demonstrated a positive feedback loop between CD4+ TH2 cells and monocytes in patients with established peanut allergy. Exposure of peanut allergen led to release of IL-4 and IL-13 from antigen-specific TH2 cells, which induced differentiation of monocytes into CD209+ monocyte-derived dendritic cells. Subsequent presentation of peanut allergens by CD209+ dendritic cells to TH2 cells then enhanced TH2 cytokine production to continue the cycle. Notably, successful oral immunotherapy in peanut-allergic patients correlated with decreased frequency of CD209+ dendritic cells. Overall, these findings identify a positive feedback loop that represents a promising therapeutic target for the treatment of food allergy.Kari C. NadeauView Large Image Figure ViewerDownload Hi-res image Download (PPT) We asked corresponding author Kari C. Nadeau, MD, PhD, of the Sean N. Parker Center for Allergy & Asthma Research at Stanford University and Division of Pulmonary, Allergy, and Critical Care Medicine, in Stanford, California, to comment on the study. She writes, “We believe this is a significant breakthrough to try to identify a target which attenuates pathological interactions between DC and T cells in human food allergy.” Multiple phase 3 randomized placebo-controlled trials examined the efficacy of upadacitinib, a selective oral inhibitor of Janus kinase 1 (JAK1), in adult and adolescent patients with moderate-to-severe atopic dermatitis. In 2 replicate 16-week trials, Guttman-Yassky et al (Lancet 2021;397:2151-68; https://doi.org/10.1016/S0140-6736(21)00588-2) identified that monotherapy with upadacitinib improved symptom and disease severity as compared to placebo. Reich et al (Lancet 2021;397:2169-81; https://doi.org/10.1016/S0140-6736(21)00589-4) found that the combination of upadacitinib and topical corticosteroids improve disease severity and symptom control as compared to placebo plus topical corticosteroids. Importantly, upadacitinib was well-tolerated in all trials. Collectively, the findings from these trials identify upadacitinib as an effective treatment for moderate-to-severe atopic dermatitis.Upadacitinib improved symptom and disease severity Upadacitinib improved symptom and disease severity Menzies-Gow et al (N Engl J Med 2021;384:1800-9; https://doi.org/10.1056/NEJMoa2034975) examined the efficacy of tezepelumab, a mAb directed against the epithelial cell-derived cytokine thymic stromal lymphopoietin, in severe uncontrolled asthma in a yearlong phase 3 randomized controlled trial. As compared to placebo, tezepelumab decreased the annualized rate of asthma exacerbations by 56% and improved lung function, asthma control, and health-related quality of life. Additionally, in a subgroup analysis tezepelumab was effective among patients with baseline low blood eosinophil counts. Importantly, tezepelumab was well-tolerated. The results of this study support the use of tezepelumab for the treatment of severe, uncontrolled asthma. Image attribution Wikimedia by user BruceBlaus, Public domain, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Asthma_(Lungs).png.Andrew Menzies-GowView Large Image Figure ViewerDownload Hi-res image Download (PPT) We asked first author Andrew Menzies-Gow, MBBS, PhD, FRCP, of Royal Brompton Hospital, London, United Kingdom, to comment on the study. He writes, “The NAVIGATOR study is an important step forward for the use of biologics in severe asthma, as it supports the ability of tezepelumab to significantly reduce exacerbations in a broad population of patients with severe uncontrolled asthma, irrespective of baseline blood eosinophil count.” Treatment with the antibiotic azithromycin reduces the duration and severity of asthma exacerbations, although the underlying mechanisms remain poorly understood. Thorsen et al (Am J Respir Crit Care Med 2021 Mar 17; https://doi.org/10.1164/rccm.202008-3226OC) performed a randomized, placebo-controlled trial examining the effect of azithromycin on the airway microbiota in a cohort of infants with recurrent asthma-like symptoms. Acute episodes were associated with increased diversity of airway microbiota. Increased airway microbial diversity correlated with the duration of episodes and enhanced the treatment effect of azithromycin. These results support the notion that azithromycin decreases the duration of acute asthma-like episodes by modulating the airway microbiota and underscore the importance of the airway microbiota during acute episodes.Hans BisgaardView Large Image Figure ViewerDownload Hi-res image Download (PPT) We asked corresponding author Hans Bisgaard, MD, DMSc, of Herlev and Gentofte Hospital, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, in Hellerup, Denmark, to comment on the study. He writes, “We have previously shown the prevalence of pathogenic bacteria is similar to that of virus in recurrent asthma-like symptoms in young children and later supported this by demonstrating the effect of azithromycin. This study lends further support to the importance of the airway microbiota during acute episodes.”News items were written by medical writer Jared Travers, MD, PhD. News items were written by medical writer Jared Travers, MD, PhD.