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| Open AccessSolar ultraviolet B radiation promotes α-MSH secretion to attenuate the function of ILC2s via the pituitary–lung axis
Allergic asthma is episodic and associated with seasonal changes which may have links with UV exposure levels. Here the authors propose a link between UVB exposure and ILC2 function through α-MSH released from the pituitary gland which accumulates in the serum and alters ILC2 function through the MC5R receptor.
- Yuying Huang
- , Lin Zhu
- & Bing Sun
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Article
| Open AccessIL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation
Interleukin 9 (IL-9) is a cytokine that plays causative role in airway inflammation of both infectious and allergic origin. Here authors show in a mouse model of SARS-CoV-2 infection that IL-9, predominantly produced by helper T cells, plays a critical pathogenic role in COVID-19 via an inflammatory pathway involving the transcription factor Foxo1.
- Srikanth Sadhu
- , Rajdeep Dalal
- & Amit Awasthi
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Article
| Open AccessHomeostatic serum IgE is secreted by plasma cells in the thymus and enhances mast cell survival
Elevated levels of IgE is associated with a range of allergic pathology but the source of such IgE producing B cells during the steady state is poorly understood. Here, Kwon et al. show that homeostatic IgE is secreted by plasma cells in the thymus and link this to mast cell survival.
- Dong-il Kwon
- , Eun Seo Park
- & You Jeong Lee
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Article
| Open AccessDisease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a progressing disease, with lung but not gut microbiota implicated in its etiology. Here the authors compare the stool from patients with COPD and healthy controls to find specific gut bacteria and metabolites associated with active disease, thereby hinting at a potential role for the gut microbiome in COPD.
- Kate L. Bowerman
- , Saima Firdous Rehman
- & Philip M. Hansbro
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Matters Arising
| Open AccessReply to “Acid inhibitors and allergy: comorbidity, causation and confusion”
- Erika Jensen-Jarolim
- , Michael Kundi
- & Galateja Jordakieva
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| Open AccessMass cytometry reveals cellular fingerprint associated with IgE+ peanut tolerance and allergy in early life
Food allergy is triggered by IgE, but some individuals are not allergic to peanuts despite making peanut-specific IgE, and are considered peanut-tolerant. Here, the authors identify differences in blood immune cell composition of peanut-allergic and tolerant infants using mass cytometry, which may help uncover the mechanism of allergic tolerance.
- Melanie R. Neeland
- , Sandra Andorf
- & Kari C. Nadeau
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Article
| Open AccessThe mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab
Immunoglobulin E (IgE) plays a central role in allergic responses, yet therapeutic targeting of IgE with antibodies such as omalizumab is met with various limitations. Here the authors characterize the molecular properties and crystal structure of a new anti-IgE antibody, ligelizumab, for mechanistic insights related to its enhanced suppression activity.
- Pascal Gasser
- , Svetlana S. Tarchevskaya
- & Alexander Eggel
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| Open AccessTreating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement
Allergen-specific immunotherapy is used to treat patients affected by acute immunoglobulin E (IgE) responses, but the function mechanism is unclear. Here the authors show that the administration of two cat allergen-specific IgGs reduces allergic responses in mouse models and helps ameliorate clinical symptoms in a phase 1b clinical trial.
- J. M. Orengo
- , A. R. Radin
- & G. D. Yancopoulos
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Article
| Open AccessTrapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcεRI interaction
IgE is linked to allergic diseases and there is a great interest in developing anti-IgE therapeutics. Here the authors characterize the binding of human IgE Fc to a single domain antibody (sdab) and show that the sdab induces a closed conformation, which prevents and disrupts IgE binding to its receptor FcεRI and abrogates allergen mediated activation.
- Frederic Jabs
- , Melanie Plum
- & Edzard Spillner
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Article
| Open AccessIntegrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions
Rising rates of peanut allergy pose a public health problem. Here, the authors profile blood transcriptomes during double-blind, placebo-controlled oral challenge in peanut-allergic children to identify gene and cell composition changes, and construct causal networks to detect key allergic reaction drivers.
- C. T. Watson
- , A. T. Cohain
- & S. Bunyavanich
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Article
| Open AccessGenome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy
Food allergy is an increasing public health problem. In a genome-wide scan of children diagnosed by oral food challenge, Marenholz et al. find new genetic associations underlying food allergy, implicating the immune system and the epithelial barrier.
- Ingo Marenholz
- , Sarah Grosche
- & Young-Ae Lee
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Article
| Open AccessIgG1 memory B cells keep the memory of IgE responses
IgE is an important mediator of protective immunity as well as allergic reaction, but how high affinity IgE antibodies are produced in memory responses is not clear. Here the authors show that IgE can be generated via class-switch recombination in IgG1 memory B cells without additional somatic hypermutation.
- Jin-Shu He
- , Sharrada Subramaniam
- & Maria A. Curotto de Lafaille
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Article
| Open AccessCre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography
Non-invasive cell tracking is a powerful method to visualize cells in vivo under physiological and pathophysiological conditions. Here Thunemann et al. generate a mouse model for in vivo tracking and quantification of specific cell types by combining a PET reporter gene with Cre-dependent activation that can be exploited for any cell population for which a Cre mouse line is available.
- Martin Thunemann
- , Barbara F. Schörg
- & Robert Feil
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PGD2 deficiency exacerbates food antigen-induced mast cell hyperplasia
Mast cells are major contributors to allergy. Here the authors show that prostaglandin D2-deficient mast cells produce more chemoattractants, promoting mast cell hyperplasia and exacerbating allergic responses in a mouse model of food allergy.
- Tatsuro Nakamura
- , Shingo Maeda
- & Takahisa Murata
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Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children
Food allergy is a growing clinical and public health burden. Here, the authors carry out a genome-wide association study in samples with well-defined allergies to a variety of foods, and identify the 6p21.32 region that significantly increases risk of developing peanut allergy.
- Xiumei Hong
- , Ke Hao
- & Xiaobin Wang
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GWAS identifies four novel eosinophilic esophagitis loci
Eosinophilic oesophagitis (EoE) is an allergic, inflammatory disorder of the oesophagus. Here the authors carry out a genome-wide association study in over 5,000 individuals and identify four genetic loci that affect the onset of EoE.
- Patrick M. A. Sleiman
- , Mei-Lun Wang
- & Hakon Hakonarson
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Nitric oxide enhances Th9 cell differentiation and airway inflammation
Th9 cells are a subset of T helper cells that protect hosts against helminthic infection, but can also mediate allergic disease through overexpression of the cytokine IL-9. Here, Niedbala et al.show that nitric oxide is a potent enhancer of Th9 differentiation via the activation of p53 protein.
- Wanda Niedbala
- , Anne-Gaelle Besnard
- & Foo Y. Liew
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Article
| Open AccessA designer cell-based histamine-specific human allergy profiler
The advancement of sensitive, accurate and non-invasive methods to identify the allergen that drives allergic disease in an individual remains a challenge. Here, the authors develop a synthetic biology approach using human designer cells to profile allergic reactions against an array of allergens measuring histamine release from whole blood.
- David Ausländer
- , Benjamin Eggerschwiler
- & Martin Fussenegger
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An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells
Contact hypersensitivity is caused by the reaction of T cells to various chemical contact allergens. Here, the authors unveil the signalling pathway induced in dendritic cells in response to contact allergens, which is required for the stimulation of T-cell sensitization in contact hypersensitivity.
- Shinsuke Yasukawa
- , Yoshiyuki Miyazaki
- & Hiromitsu Hara
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Nucleic acid sensing by T cells initiates Th2 cell differentiation
Nucleic acids modulate T cell responses; however, the physiological significance of this property remains unclear. Here, the authors show that self-DNA complexes with antimicrobial peptides or histones, which mediates T cell costimulation to induce Th2 cell differentiation.
- Takayuki Imanishi
- , Chitose Ishihara
- & Takashi Saito
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Two potential therapeutic antibodies bind to a peptide segment of membrane-bound IgE in different conformations
Two antibodies targeting the CεmX domain of membrane-bound IgE on human B lymphocytes are being developed to treat allergy. Here, the authors map the antigenic epitopes of the two antibodies and show that they bind to different conformations of the same peptide region.
- Hsing-Mao Chu
- , Jon Wright
- & Carmay Lim
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Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation
Inositol polyphosphate 4 phosphatase regulates phosphoinositide signalling and is associated with an increased risk of asthma. Aichet al. show that, in a mouse model of airway inflammation, calpains degrade inositol polyphosphate 4 phosphatase resulting in exacerbated phosphoinositide 3-kinase signalling.
- Jyotirmoi Aich
- , Ulaganathan Mabalirajan
- & Balaram Ghosh