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pubmed: 0091-6749



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Eosinophils and Eosinophil-Associated Diseases: an Update.
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Eosinophils and Eosinophil-Associated Diseases: an Update.

J Allergy Clin Immunol. 2017 Oct 15;:

Authors: O'Sullivan JA, Bochner BS

Abstract
The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the broad field of allergy and immunology. This particular assignment was to cover the topic of eosinophils. In an attempt to highlight major ideas, themes, trends and advances relevant to basic and clinical aspects of eosinophil biology, a search of papers published since 2015 in JACI and other high impact journals was performed. Manuscripts were then reviewed and organized, and then key findings were summarized. Given space limitations, many outstanding papers could not be included, but the hope is that what follows provides a succinct overview of recently published work that has significantly added to our knowledge of eosinophils and eosinophil-associated diseases.

PMID: 29045815 [PubMed - as supplied by publisher]




Advances in mechanisms of allergic disease in 2016.
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Advances in mechanisms of allergic disease in 2016.

J Allergy Clin Immunol. 2017 Oct 13;:

Authors: Rothenberg ME, Saito H, Peebles RS

Abstract
This review highlights advances in mechanisms of allergic disease, particularly type 2 innate lymphoid cells; TH2 lymphocytes; eicosanoid regulation of inflammation; extracellular vesicles in allergic responses; IL-33; microbiome properties, especially as they relate to mucosal barrier function; and a series of findings concerning the allergic inflammatory cells eosinophils, basophils, and mast cells. During the last year, mechanistic advances occurred in understanding type 2 innate lymphoid cells, particularly related to their response to ozone, involvement with experimental food allergy responses, and regulation by IL-33. Novel ways of regulating TH2 cells through epigenetic regulation of GATA-3 through sirtuin-1, a class III histone deacetylase, were published. The understanding of eicosanoid regulation of inflammation increased and focused on additional properties of phospholipase A2 and the role of prostaglandin D2 and its receptors and inhibitory prostaglandin E2 pathways. Mechanisms through which extracellular vesicles are released and contribute to allergic responses were reported. There was a deeper appreciation of mucosal barrier function, the epithelial alarmin IL-33, and the microbiome. Finally, there were advances concerning allergic inflammatory cells (mast cells, basophils, and eosinophils) that will undoubtedly have an effect on disease understanding and new therapeutic strategies.

PMID: 29038009 [PubMed - as supplied by publisher]




Fibrinogen-cleavage products and TLR4 promote the generation of programmed cell death 1 ligand 2(PD-L2)+ dendritic cells in allergic asthma.
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Fibrinogen-cleavage products and TLR4 promote the generation of programmed cell death 1 ligand 2(PD-L2)+ dendritic cells in allergic asthma.

J Allergy Clin Immunol. 2017 Oct 13;:

Authors: Cho M, Lee JE, Lim H, Shin HW, Khalmuratova R, Choi G, Kim HS, Choi WS, Park YJ, Shim I, Kim BS, Kang CY, Kim JO, Tanaka S, Kubo M, Chung Y

Abstract
BACKGROUND: Inhaled protease allergens preferentially trigger Th2-mediated inflammation in allergic asthma. The role of dendritic cells (DCs) on the induction of Th2 cell responses in allergic asthma has been well documented; however, the mechanism by which protease allergens induce Th2-favorable DCs in the airway remains unclear.
OBJECTIVE: We sought to determine a subset of DCs responsible for Th2 cell responses in allergic asthma and the mechanism by which protease allergens induce the DC subset in the airway.
METHODS: Mice were intranasally challenged with protease allergens or fibrinogen-cleavage product (FCP) to induce allergic airway inflammation. DCs isolated from the mediastinal lymph nodes were analyzed for surface phenotype and T cell stimulatory function. Anti-Thy1.2 and Mas-TRECK mice were used to deplete innate lymphoid cells and mast cells, respectively. Adoptive cell transfer, bone marrow DC culture, anti-IL-13, and TLR4-deficient mice were used for further mechanistic studies.
RESULTS: Protease allergens induced a remarkable accumulation of Th2-favorable PD-L2(+) DCs in the mediastinal lymph nodes, which was significantly abolished in mice depleted of mast cells and, to a lesser extent, innate lymphoid cells. Mechanistically, FCP generated by protease allergens triggered IL-13 production from wild-type mast cells but not from TLR4-deficient mast cells, which resulted in the increase of PD-L2(+) DCs. Intranasal administration of FCP induced an increase of PD-L2(+) DCs in the airway, which was significantly abolished in TLR4- and mast cell-deficient mice. Injection of IL-13 restored PD-L2(+) DC population in mice lacking mast cells.
CONCLUSION: Our findings unveil the 'protease-FCP-TLR4-mast cell-IL-13' axis as a molecular mechanism for the generation of Th2-favorable PD-L2(+) DCs in allergic asthma, and suggest that targeting PD-L2(+) DC pathway might be effective in suppressing allergic T cell responses in the airway.

PMID: 29038008 [PubMed - as supplied by publisher]




Transcriptional determinants of individualized inflammatory responses at anatomically separate sites.
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Transcriptional determinants of individualized inflammatory responses at anatomically separate sites.

J Allergy Clin Immunol. 2017 Oct 12;:

Authors: Tsoi LC, Yang J, Liang Y, Sarkar MK, Xing X, Beamer MA, Aphale A, Raja K, Kozlow JH, Getsios S, Voorhees JJ, Kahlenberg JM, Elder JT, Gudjonsson JE

PMID: 29031600 [PubMed - as supplied by publisher]




Interaction of DJ-1 with Lyn is essential for IgE-mediated stimulation of human mast cells.
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Interaction of DJ-1 with Lyn is essential for IgE-mediated stimulation of human mast cells.

J Allergy Clin Immunol. 2017 Oct 12;:

Authors: Kim DK, Beaven MA, Metcalfe DD, Olivera A

Abstract
BACKGROUND: DJ-1 is a redox-sensitive protein with multiple roles in cell homeostasis whose levels are altered in mast cell (MC)-related disorders. However, whether DJ-1 can regulate human MC function is unknown.
OBJECTIVE: We sought to investigate the potential role of DJ-1 in the responses of human MCs to antigen stimulation.
METHODS: DJ-1 was silenced in human CD34(+)-derived and LAD2 MCs using lentiviral sh-RNA constructs. Release of β-hexosaminidase, PGD2 and GM-CSF and changes in reactive oxygen species (ROS) levels were measured after FcεRI engagement. Enzymatic assays, sucrose density gradient centrifugation, immunoprecipitations, dot and Western blots, and confocal imaging were performed for signaling, cellular localization and co-association studies.
RESULTS: DJ-1 knockdown substantially reduced mediator release as well as Lyn and Syk kinase activation and signaling by mechanisms which appeared largely unrelated to DJ-1 antioxidant activity. Upon FcεRI activation, non-oxidized rather than oxidized DJ-1 translocated to lipid rafts where it associated with Lyn, an interaction that appeared critical for maximal Lyn activation and initiation of signaling. Using purified recombinant proteins, we demonstrated that DJ-1 bound to Lyn directly but no other Src kinases, and this interaction was specific for human but not mouse proteins. In addition, DJ-1 reduced SHP-2 phosphatase activity by scavenging ROS thus preventing Syk dephosphoryation and perpetuating MC signaling.
CONCLUSION: We demonstrate a novel role for DJ-1 in the early activation of Lyn by FcεRI that is essential for human MC responses and which provides the basis for an alternative target in allergic diseases therapy.

PMID: 29031599 [PubMed - as supplied by publisher]




Clinical relevance of sensitization to hydrolyzed wheat protein in wheat-sensitized individuals.
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Clinical relevance of sensitization to hydrolyzed wheat protein in wheat-sensitized individuals.

J Allergy Clin Immunol. 2017 Oct 12;:

Authors: Christensen MJ, Stahl Skov P, Poulsen LK, Bindslev-Jensen C, Mortz CG

PMID: 29031598 [PubMed - as supplied by publisher]




Lower Airway Microbiota and Mycobiota in Children with Severe Asthma.
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Lower Airway Microbiota and Mycobiota in Children with Severe Asthma.

J Allergy Clin Immunol. 2017 Oct 12;:

Authors: Goldman DL, Chen Z, Shankar V, Tyberg M, Vicencio A, Burk R

PMID: 29031597 [PubMed - as supplied by publisher]




Lolium perenne peptides for treatment of grass pollen allergy: A randomized, double-blind, placebo-controlled clinical trial.
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Lolium perenne peptides for treatment of grass pollen allergy: A randomized, double-blind, placebo-controlled clinical trial.

J Allergy Clin Immunol. 2017 Oct 10;:

Authors: Shamji MH, Ceuppens J, Bachert C, Hellings P, Placier G, Thirion G, Bovy N, Durham SR, Duchateau J, Legon T, Pirotton S

PMID: 29030102 [PubMed - as supplied by publisher]




Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes c11orf30/EMSY as a genetic risk factor for food allergy.
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Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes c11orf30/EMSY as a genetic risk factor for food allergy.

J Allergy Clin Immunol. 2017 Oct 10;:

Authors: Asai Y, Eslami A, van Ginkel CD, Akhabir L, Wan M, Ellis G, Ben-Shoshan M, Martino D, Ferreira MA, Allen K, Mazer B, de Groot H, de Jong NW, Gerth van Wijk RN, Dubois AEJ, Chin R, Cheuk S, Hoffman J, Jorgensen E, Witte JS, Melles RB, Hong X, Wang X, Hui J, Musk AWB, Hunter M, James AL, Koppelman GH, Sandford AJ, Clarke AE, Daley D

Abstract
BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously PA loci were identified in FLG and HLA in candidate gene studies, and loci in HLA in a genome-wide association study and meta-analysis.
OBJECTIVE: To investigate genetic susceptibility to PA.
METHODS: Eight hundred and fifty cases and 926 hyper-controls and >7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. Meta-analysis of two phenotypes (PA and food allergy) was conducted using 7 studies from the Canadian, American (2), Australian, German and Dutch (2) populations.
RESULTS: A SNP near ITGA6 reached genome-wide significance with PA (p=1.80×10(-8)), while SNPs associated with SKAP1, MMP12/MMP13, CTNNA3, ARHGAP24, ANGPT4, c11orf30 (EMSY), and EXOC4 reached a threshold suggestive of association (p≤1.49×10(-6)). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, c11orf30 and EXOC4 were significant (p≤1.49×10(-6)). When a phenotype of any food allergy was used for meta-analysis, the c11orf30 locus reached genome-wide significance (p=7.50×10(-11)), while SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, EXOC4 and additional c11orf30 SNPs were suggestive (p≤1.49×10(-6)). Functional annotation indicated SKAP1 regulates expression of CBX1, which co-localizes with the EMSY protein coded by c11orf30.
CONCLUSION: This study identifies multiple novel loci as risk factors for PA and food allergy and establishes c11orf30 as a risk locus for both peanut and food allergy. Multiple genes (c11orf30/EMSY, SKAP1 and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.

PMID: 29030101 [PubMed - as supplied by publisher]




Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis.
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Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis.

J Allergy Clin Immunol. 2017 Sep 12;:

Authors: Jensen ET, Kuhl JT, Martin LJ, Langefeld CD, Dellon ES, Rothenberg ME

Abstract
BACKGROUND: Although eosinophilic esophagitis (EoE) is associated with certain gene variants, the rapidly increasing incidence of EoE suggests that environmental factors contribute to disease development.
OBJECTIVE: We tested for gene-environment interaction between EoE-predisposing polymorphisms (within TSLP, LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit [NICU] admission, and absence of pets in the home).
METHODS: We conducted a case-control study using hospital-based cases (n = 127) and control subjects representative of the hospital catchment area (n = 121). We computed case-only interaction tests and in secondary analyses evaluated the combined and independent effects of genotype and environmental factors on the risk of EoE.
RESULTS: Case-only analyses identified interactions between rs6736278 (CAPN14) and breast-feeding (P = .02) and rs17815905 (LOC283710/KLF13) and NICU admission (P = .02) but not with any of the factors examined. Case-control analyses suggested that disease risk might be modifiable in subjects with certain gene variants. In particular, breast-feeding in those with the susceptibility gene variant at rs6736278 (CAPN14) reduced the risk of EoE (adjusted odds ratio, 0.08; 95% CI, 0.01-0.59). Admission to the NICU in those without the susceptibility gene variant at rs17815905 (LOC283710/KLF13) significantly increased the risk of having disease (adjusted odds ratio, 4.83; 95% CI, 1.49-15.66).
CONCLUSIONS: The interplay of gene (CAPN14 and LOC283710/KLF13) and early-life environment factors (breast-feeding and NICU admission) might contribute to EoE susceptibility.

PMID: 29029802 [PubMed - as supplied by publisher]