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

Childhood factors leading to severe asthma later in lifeIzadi et al (Am J Respir Crit Care Med 2021 May 24; https://doi.org/10.1164/rccm.202010-3763OC) utilized data from the Childhood Asthma Management Program longitudinal cohort, which consists of pediatric subjects with mild-to-moderate asthma, in order to identify the childhood factors that predict the development of severe persistent asthma later in life. Low post-bronchodilator FEV1/FVC ratio and maternal smoking during pregnancy significantly increased the risk of developing persistent severe asthma from late adolescence into early adulthood. These results suggest that early decline in lung function drives persistence of severe asthma. The authors propose that early interventions in childhood to preserve lung function may help prevent disease progression although further investigation is needed.Neema IzadiView Large Image Figure ViewerDownload Hi-res image Download (PPT)Dietary effects on gut microbiota modulate inflammation systemicallyHigh-fermented-food diet increased microbial diversity and decreased serum levels of inflammatory cytokinesView Large Image Figure ViewerDownload Hi-res image Download (PPT)Sympathetic nervous system activation impairs immunityView Large Image Figure ViewerDownload Hi-res image Download (PPT)Devi et al (Immunity 2021;54:1219-30.e7; https://doi.org/10.1016/j.immuni.2021.03.025) discovered a link between activation of the sympathetic nervous system and compromised immunity. More specifically, injection of noradrenaline transiently inhibited the movement of CD4+ and CD8+ T cells in tissues as assessed by intravital 2-photon microscopy. Activation of the sympathetic nervous system in chemogenetic mice or through adrenergic receptor agonists decreased blood flow to lymph nodes, and the subsequent transient hypoxia inhibited leukocyte motility by triggering calcium signaling. Notably, the impaired leukocyte motility was reversed with oxygen supplementation. In total, these results identify adrenergic signaling as a novel potential therapeutic target for modulation of T cell responses. Several videos from the article are of particular interest and can be viewed at the following links: https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc2.mp4, https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc7.mp4, https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc8.mp4. Image attribution Wikimedia by user Dana Scarinci Zabaleta, CC0, https://commons.wikimedia.org/wiki/File:Two_neurons_connected.svg, via Wikimedia Commons.Scott N. MuellerView Large Image Figure ViewerDownload Hi-res image Download (PPT)Esophagus-resident pathogenic effector T cells in eosinophilic esophagitisView Large Image Figure ViewerDownload Hi-res image Download (PPT)Utilizing single-cell RNA and T-cell receptor (TCR) sequencing, Morgan et al (Sci Immunol 2021;6:eabi5586; https://doi.org/10.1126/sciimmunol.abi5586) characterized the T-cell populations of patients with eosinophilic esophagitis (EoE). During active disease, esophagus-resident pathogenic effector TH2 (peTH2) cells were present with evidence of clonal expansion, suggesting antigen-induced activation. Peripheral blood memory peTH2 cells with clonal expansion and convergent TCR sequences were also identified in the peripheral blood during active disease and expressed a homing receptor GPR15 potentially involved in the esophagus. Notably, GPR15-expressing peTH2 cells were enriched among CD4+ T cells reactive to milk protein in patients with known milk-triggered disease. Collectively, these findings identify GPR15-expressing peTH2 cells as a prominent cellular population with food antigen-induced clonal expansion in active EoE and may contribute to disease pathogenesis. Image attribution Wikimedia by CoRus13, CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Eosinophilic_esophagitis,_very_high_mag.1.jpg, via Wikimedia Commons.Targeting TSLP decreases airway eosinophilia and hyperresponsiveness in asthmaView Large Image Figure ViewerDownload Hi-res image Download (PPT)The thymic stromal lymphopoietin (TSLP)-neutralizing mAb tezepelumab has previously been shown to reduce severe asthma exacerbations irrespective of level of type 2 inflammation. Diver et al (Lancet Respir Med 2021 Jul 9; https://doi.org/10.1016/S2213-2600(21)00226-5) performed a mechanistic randomized, placebo-controlled trial (CASCADE) to determine the effects of tezepelumab on airway immune cells, remodeling, and hyperresponsiveness. Regardless of baseline peripheral blood eosinophil counts, tezepelumab decreased submucosal levels of eosinophils but not of other inflammatory cell types. Additionally, tezepelumab reduced airway hyperresponsiveness without exerting significant effects on airway remodeling. The findings from this study suggest that the therapeutic benefits of tezepelumab in asthma likely occur by decreasing eosinophilic inflammation and airway hyperresponsiveness.Christopher E. BrightlingView Large Image Figure ViewerDownload Hi-res image Download (PPT)News items were written by medical writer Jared Travers, MD, PhD. Childhood factors leading to severe asthma later in lifeIzadi et al (Am J Respir Crit Care Med 2021 May 24; https://doi.org/10.1164/rccm.202010-3763OC) utilized data from the Childhood Asthma Management Program longitudinal cohort, which consists of pediatric subjects with mild-to-moderate asthma, in order to identify the childhood factors that predict the development of severe persistent asthma later in life. Low post-bronchodilator FEV1/FVC ratio and maternal smoking during pregnancy significantly increased the risk of developing persistent severe asthma from late adolescence into early adulthood. These results suggest that early decline in lung function drives persistence of severe asthma. The authors propose that early interventions in childhood to preserve lung function may help prevent disease progression although further investigation is needed. Izadi et al (Am J Respir Crit Care Med 2021 May 24; https://doi.org/10.1164/rccm.202010-3763OC) utilized data from the Childhood Asthma Management Program longitudinal cohort, which consists of pediatric subjects with mild-to-moderate asthma, in order to identify the childhood factors that predict the development of severe persistent asthma later in life. Low post-bronchodilator FEV1/FVC ratio and maternal smoking during pregnancy significantly increased the risk of developing persistent severe asthma from late adolescence into early adulthood. These results suggest that early decline in lung function drives persistence of severe asthma. The authors propose that early interventions in childhood to preserve lung function may help prevent disease progression although further investigation is needed. Dietary effects on gut microbiota modulate inflammation systemically Sympathetic nervous system activation impairs immunityDevi et al (Immunity 2021;54:1219-30.e7; https://doi.org/10.1016/j.immuni.2021.03.025) discovered a link between activation of the sympathetic nervous system and compromised immunity. More specifically, injection of noradrenaline transiently inhibited the movement of CD4+ and CD8+ T cells in tissues as assessed by intravital 2-photon microscopy. Activation of the sympathetic nervous system in chemogenetic mice or through adrenergic receptor agonists decreased blood flow to lymph nodes, and the subsequent transient hypoxia inhibited leukocyte motility by triggering calcium signaling. Notably, the impaired leukocyte motility was reversed with oxygen supplementation. In total, these results identify adrenergic signaling as a novel potential therapeutic target for modulation of T cell responses. Several videos from the article are of particular interest and can be viewed at the following links: https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc2.mp4, https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc7.mp4, https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc8.mp4. Image attribution Wikimedia by user Dana Scarinci Zabaleta, CC0, https://commons.wikimedia.org/wiki/File:Two_neurons_connected.svg, via Wikimedia Commons.Scott N. MuellerView Large Image Figure ViewerDownload Hi-res image Download (PPT) Devi et al (Immunity 2021;54:1219-30.e7; https://doi.org/10.1016/j.immuni.2021.03.025) discovered a link between activation of the sympathetic nervous system and compromised immunity. More specifically, injection of noradrenaline transiently inhibited the movement of CD4+ and CD8+ T cells in tissues as assessed by intravital 2-photon microscopy. Activation of the sympathetic nervous system in chemogenetic mice or through adrenergic receptor agonists decreased blood flow to lymph nodes, and the subsequent transient hypoxia inhibited leukocyte motility by triggering calcium signaling. Notably, the impaired leukocyte motility was reversed with oxygen supplementation. In total, these results identify adrenergic signaling as a novel potential therapeutic target for modulation of T cell responses. Several videos from the article are of particular interest and can be viewed at the following links: https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc2.mp4, https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc7.mp4, https://ars.els-cdn.com/content/image/1-s2.0-S1074761321001370-mmc8.mp4. Image attribution Wikimedia by user Dana Scarinci Zabaleta, CC0, https://commons.wikimedia.org/wiki/File:Two_neurons_connected.svg, via Wikimedia Commons. Esophagus-resident pathogenic effector T cells in eosinophilic esophagitisUtilizing single-cell RNA and T-cell receptor (TCR) sequencing, Morgan et al (Sci Immunol 2021;6:eabi5586; https://doi.org/10.1126/sciimmunol.abi5586) characterized the T-cell populations of patients with eosinophilic esophagitis (EoE). During active disease, esophagus-resident pathogenic effector TH2 (peTH2) cells were present with evidence of clonal expansion, suggesting antigen-induced activation. Peripheral blood memory peTH2 cells with clonal expansion and convergent TCR sequences were also identified in the peripheral blood during active disease and expressed a homing receptor GPR15 potentially involved in the esophagus. Notably, GPR15-expressing peTH2 cells were enriched among CD4+ T cells reactive to milk protein in patients with known milk-triggered disease. Collectively, these findings identify GPR15-expressing peTH2 cells as a prominent cellular population with food antigen-induced clonal expansion in active EoE and may contribute to disease pathogenesis. Image attribution Wikimedia by CoRus13, CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Eosinophilic_esophagitis,_very_high_mag.1.jpg, via Wikimedia Commons. Utilizing single-cell RNA and T-cell receptor (TCR) sequencing, Morgan et al (Sci Immunol 2021;6:eabi5586; https://doi.org/10.1126/sciimmunol.abi5586) characterized the T-cell populations of patients with eosinophilic esophagitis (EoE). During active disease, esophagus-resident pathogenic effector TH2 (peTH2) cells were present with evidence of clonal expansion, suggesting antigen-induced activation. Peripheral blood memory peTH2 cells with clonal expansion and convergent TCR sequences were also identified in the peripheral blood during active disease and expressed a homing receptor GPR15 potentially involved in the esophagus. Notably, GPR15-expressing peTH2 cells were enriched among CD4+ T cells reactive to milk protein in patients with known milk-triggered disease. Collectively, these findings identify GPR15-expressing peTH2 cells as a prominent cellular population with food antigen-induced clonal expansion in active EoE and may contribute to disease pathogenesis. Image attribution Wikimedia by CoRus13, CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Eosinophilic_esophagitis,_very_high_mag.1.jpg, via Wikimedia Commons. Targeting TSLP decreases airway eosinophilia and hyperresponsiveness in asthmaThe thymic stromal lymphopoietin (TSLP)-neutralizing mAb tezepelumab has previously been shown to reduce severe asthma exacerbations irrespective of level of type 2 inflammation. Diver et al (Lancet Respir Med 2021 Jul 9; https://doi.org/10.1016/S2213-2600(21)00226-5) performed a mechanistic randomized, placebo-controlled trial (CASCADE) to determine the effects of tezepelumab on airway immune cells, remodeling, and hyperresponsiveness. Regardless of baseline peripheral blood eosinophil counts, tezepelumab decreased submucosal levels of eosinophils but not of other inflammatory cell types. Additionally, tezepelumab reduced airway hyperresponsiveness without exerting significant effects on airway remodeling. The findings from this study suggest that the therapeutic benefits of tezepelumab in asthma likely occur by decreasing eosinophilic inflammation and airway hyperresponsiveness.Christopher E. BrightlingView Large Image Figure ViewerDownload Hi-res image Download (PPT)News items were written by medical writer Jared Travers, MD, PhD. The thymic stromal lymphopoietin (TSLP)-neutralizing mAb tezepelumab has previously been shown to reduce severe asthma exacerbations irrespective of level of type 2 inflammation. Diver et al (Lancet Respir Med 2021 Jul 9; https://doi.org/10.1016/S2213-2600(21)00226-5) performed a mechanistic randomized, placebo-controlled trial (CASCADE) to determine the effects of tezepelumab on airway immune cells, remodeling, and hyperresponsiveness. Regardless of baseline peripheral blood eosinophil counts, tezepelumab decreased submucosal levels of eosinophils but not of other inflammatory cell types. Additionally, tezepelumab reduced airway hyperresponsiveness without exerting significant effects on airway remodeling. The findings from this study suggest that the therapeutic benefits of tezepelumab in asthma likely occur by decreasing eosinophilic inflammation and airway hyperresponsiveness. News items were written by medical writer Jared Travers, MD, PhD. News items were written by medical writer Jared Travers, MD, PhD.