News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2019)

The immune responses underlying viral and nonviral asthma exacerbations have been more deeply solved though systems-scale transcriptional network analyses of nasal and blood samples obtained from children with virus-triggered asthma by Altman et al (Nat Immunol 201;20:637-51; https://doi.org/10.1038/s41590-019-0347-8). Both viral and nonviral exacerbations exhibited activation of a core set of transcriptional programs, including epithelium-associated SMAD3 signaling, epidermal growth factor receptor signaling, eosinophil activation, and production of mucus and extracellular matrix. Interestingly, nonviral asthma exacerbations exhibited upregulation of squamous cell pathways, whereas multiple inflammatory cell pathways were uniquely associated with viral exacerbations. Thus catching a cold can be transcriptionally quite costly. Figure attribution: Public Domain at Wikimedia Commons by user BruceBlaus [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)].Multiple inflammatory cell pathways were uniquely associated with viral exacerbations Multiple inflammatory cell pathways were uniquely associated with viral exacerbations Svedberg et al (Nat Immunol 2019;20:571-80; https://doi.org/10.1038/s41590-019-0352-y) have determined that lung microenvironment–driven changes in the cellular metabolism of macrophages alter their activation during type 2 inflammation. Alveolar macrophages were found to be hyporesponsive to IL-4 compared with macrophages obtained from lung tissue or peritoneal cavity. This hyporesponsiveness was driven by dysregulated metabolism, including impaired glycolysis, within the alveolar macrophages, and full IL-4 responsiveness caused by return of glycolysis was regained on removal from the lungs. Collectively, these results demonstrate that the pulmonary microenvironment modulates lung macrophage responses during type 2 immunity through energy metabolism.The pulmonary microenvironment modulates lung macrophage responses during type 2 immunity, through energy metabolism The pulmonary microenvironment modulates lung macrophage responses during type 2 immunity, through energy metabolism We asked authors Peter C. Cook, PhD, and Andrew S. MacDonald, PhD, of the University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom, to comment on the study. They wrote, “Respiratory type 2 mediated illnesses, such as asthma attacks and potentially deadly parasitic infections, cause terrible suffering in both the developing and developed world. The prospect of future treatments for such conditions that modify metabolism in the lung microenvironment to improve airway macrophage responses is tremendously exciting.” Lachowicz-Scroggins et al (Am J Respir Crit Care Med 2019; https://doi.org/10.1164/rccm.201810-1869OC) measured extracellular DNA-containing neutrophil extracellular traps in sputum samples of 399 patients with severe asthma. Sputum extracellular DNA traps were associated with worse asthma control, neutrophilic inflammation in the airways, increased caspase 1 activity, and IL-1β release. Neutrophil extracellular traps induced cell death of airway epithelial cells in vitro, which was prevented by treatment with the DNA-degrading enzyme deoxyribonuclease. Thus modulating DNA traps might have potential to improve asthma control.Extracellular DNA traps were associated with worse asthma control Extracellular DNA traps were associated with worse asthma control Tissue-resident T lymphocytes exhibit substantial heterogeneity and have critical yet incompletely defined roles in allergic disorders. Using the tissue-specific allergic disease eosinophilic esophagitis (EoE) as a model, Wen et al (J Clin Invest 2019; https://doi.org/10.1172/JCI125917) used single-cell RNA sequencing to generate transcription profiles of 1088 individual esophageal epithelium–derived T cells from biopsy specimens of patients with EoE. Eight distinct T-cell subtypes (designated T1-T8) were identified. The T7 and T8 clusters were enriched in patients with EoE and resembled regulatory T and effector TH2 cells, respectively. T8 cells uniquely produced copious amounts of IL-5 and IL-13 and exhibited increased expression of the short-chain fatty acid receptor FFAR3 compared with T7 cells. Furthermore, FFAR3 ligands induced TH2 cytokine production from T cells in vitro and in vivo. Through this study, the authors have elegantly characterized distinct esophageal T-cell populations in patients with EoE on a single-cell basis and have provided a resource to further dissect the importance of tissue-resident lymphocytes and genome-wide molecular mechanisms in allergic disorders. Figure attribution: Public Domain at Wikimedia Commons by user Thomas Shafee [CC BY 4.0 (https://creativecommons.org/licenses/by/4.0)].Distinct esophageal T-cell populations in patients with EoE on a single-cell basis Distinct esophageal T-cell populations in patients with EoE on a single-cell basis We asked first author Ting Wen, MD, PhD, of Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, to comment on the study. Professor Wen writes, “Leveraged on the new technology platform that our team has developed during the past 8 years, this is the first opportunity that we have ever had to look into the fundamental wiring and configuration of these extremely powerful tissue-resident TH2 cells in allergic tissue that can misbehave and cause a huge degree of suffering.” Because little is known about the effects of long-duration space missions on human health, Garrett-Bakelman et al (Science 2019;364; https://science.sciencemag.org/content/364/6436/eaau8650.long) performed a comprehensive multidimensional analysis of the changes that occurred in an astronaut who spent a year in outer space, with his identical twin serving as a genetically matched control subject. Among a plethora of other effects, spending a year in space altered the astronaut’s expression of inflammatory cytokines and immune response gene networks in peripheral blood samples. Importantly, an appropriate T-cell response to an influenza vaccination in space was observed. These results highlight the need for further investigation into the effects of extended space exposures on human health, including immunity. I would like to congratulate Dr Jared Travers for completing his MD/PhD training at the University of Cincinnati in addition to assisting with writing the “News Beyond Our Pages” columns. He will next begin a research track residency in Internal Medicine at Case Western Reserve University as part of the Harrington Physician-Scientist Pathway and plans to pursue fellowship training in Gastroenterology. Keep up the strong work! Marc Rothenberg MD, PhD Associate Editor, JACINews items were written by medical writer Jared Travers, MD, PhD. News items were written by medical writer Jared Travers, MD, PhD.