Mechanisms of allergen-specific B cell tolerance in children with cow’s milk-oral immunotherapy and natural outgrowth of milk allergy
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB48819 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR7429770.fastq.gz | Fastqsanger.gz | |||
| ERR7429780.fastq.gz | Fastqsanger.gz | |||
| ERR7429790.fastq.gz | Fastqsanger.gz | |||
| ERR7429800.fastq.gz | Fastqsanger.gz | |||
| ERR7429771.fastq.gz | Fastqsanger.gz |
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Project description:This study was conducted in order to gain insight into microbial and functional differences related to outgrowth of cow’s milk allergy (CMA) and a nutritional intervention with synbiotics.
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Project description:Goat’s milk (GM), as compared to Cow’s milk (CM), is easier for human to digest and absorb. GM feeding can improve colic, minor digestive disorders, asthma or eczema in infants. It has been demonstrated that GM have antioxidant and anti-inflammatory effects. Whether GM consumed in pregnant mothers has any immune-modulating effects on their newborns is still unclear. In this study, we used pregnant mothers and their offspring mice to verify this hypothesis. we collected feces of offspring before allergen sensitization (day 0) and two days after i.t. allergen challenge (day 16). Detection of cDNA of feces using Applied Biosystems™ Axiom™ Microbiome Array found the phyla of Bacteroidia, Clostridia, Flavobacteriia, Deferribacteres, Verrucomicrobiae and Gammaproteobacteria as well as some unclassified viruses. Comparison in ratio of Firmicutes to Bacteroidetes (F/B ratio), water-fed (W0) group had higher F/B ratio (0.79) than GM-fed (G0) (0.50) and CM-fed (C0) group (0.54) at Day 0. After HDM allergen sensitization and challenge, there was a remarkable increase of F/B ratio in water-fed mice (0.63 in WN vs. 0.84 in WA), while there was no change of F/B ratio in GM-fed (GN vs. GA) and CM-fed mice (CN vs. CA)
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Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
2020-06-10 | GSE146170 | GEO
Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
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Project description:Study of children with Cow's Milk Allergy
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Project description:Exclusively breast-fed infants can exhibit clear signs of IgE or non IgE-mediated cow’s milk allergy. The definite characterization of dietary cow’s milk proteins (CMP) that survive the maternal digestive tract to be absorbed into the bloodstream and secreted into breast milk remains missing. The aim of this study was to assess the occurrence of CMP-derived peptides in breast milk, using antibody-independent methods. Using high performance liquid chromatography-high resolution mass spectrometry in blinded assays, we identified 11 cow’s milk-derived peptides, including two β-lactoglobulin (2 out 6 samples) and one αs1-casein (1 out 6 samples) fragments, in breast milk from mothers receiving a cup of bovine milk daily. The β-lactoglobulin (β-Lg) fragments, namely f42-54 and f42-57, were absent in milk from mothers who observed a strict dairy-free diet (6 samples). In contrast, neither intact nor hydrolyzed β-Lg was detected by Western blot or competitive ELISA tests. CMP-derived peptides rather than intact CMP may sensitize or elicit allergic responses in the neonate through mother’s milk. Immunologically active peptides from the maternal diet could be involved in priming the newborn’s immune system to drive tolerogenic response in neonates and infants.
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Project description:Cow milk (CM) allergy is the most prevalent food allergy in young children in the US and Great Britain. Current diagnostic tests are either unreliable (IgE, skin prick test), or resource-intensive with risks (food challenges). Here we set out to determine if allergen-specific T cells in cow milk allergic (CMA) patients have a distinct quality and/or quantity that could potentially be used as a diagnostic marker. Starting from cow milk extract, we mapped T cell responses to a set of reactive epitopes that we compiled in a peptide pool. This pool induced cytokine responses in in vitro cultured cells distinguishing allergic from non-allergic subjects. Using single-cell RNA and paired TCR sequencing we detected significant changes in the transcriptional program and clonality of cow milk antigen-specific (CM+) T cells elicited by the pool in allergic vs. non-allergic subjects ex vivo. CM+ T cells from allergic subjects had increased percentages of FOXP3+ over FOXP3- cells. FOXP3+ cells are often equated with regulatory T cells (Tregs) that have suppressive activity, but CM+ FOXP3+ cells from allergic subjects showed significant expression of interferon-responsive genes and dysregulated chemokine receptor expression compared to non-allergic subjects, suggesting that these are not conventional Tregs. The CM+ FOXP3+ cells were also more clonally expanded than the FOXP3- population. We were further able to utilize surface markers (CD25, CD127, CCR7) in combination with our peptide pool stimulation to quantify these CM+ FOXP3+ cells by a simple flow cytometry assay. We show increased percentages of CM+ CD127-CD25+ cells from CMA subjects in an independent cohort, which could be used for diagnostic purposes. Looking specifically for Th2 cells normally associated with allergic diseases, we found a small population of clonally expanded CM+ cells that were significantly increased in CMA subjects and that had high expression of Th2 cytokines and pathogenic Th2/Tfh markers. Overall, these findings suggest that there are several differences in the phenotype of CM+ T cells with CM allergy and that the increase in CM+ FOXP3+ cells is a potential diagnostic marker of an allergic state. Such markers have promising applications in monitoring natural disease outgrowth and/or the efficacy of immunotherapy that will need to be validated in future studies.
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Project description:The aim of this study was to investigate how the human milk proteome relates to allergy of the mother and allergy development in the infant.
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Project description:Exclusively breast-fed infants can exhibit clear signs of IgE or non IgE-mediated cow’s milk allergy. The definite characterization of dietary cow’s milk proteins (CMP) that survive the maternal digestive tract to be absorbed into the bloodstream and secreted into breast milk remains missing. The aim of this study was to assess the occurrence of CMP-derived peptides in breast milk, using antibody-independent methods. Using high performance liquid chromatography-high resolution mass spectrometry in blinded assays, we identified 11 cow’s milk-derived peptides, including two ?-lactoglobulin (2 out 6 samples) and one ?s1-casein (1 out 6 samples) fragments, in breast milk from mothers receiving a cup of bovine milk daily. The ?-lactoglobulin (?-Lg) fragments, namely f42-54 and f42-57, were absent in milk from mothers who observed a strict dairy-free diet (6 samples). In contrast, neither intact nor hydrolyzed ?-Lg was detected by Western blot or competitive ELISA tests. CMP-derived peptides rather than intact CMP may sensitize or elicit allergic responses in the neonate through mother’s milk. Immunologically active peptides from the maternal diet could be involved in priming the newborn’s immune system to drive tolerogenic response in neonates and infants.
2017-04-02 | MSV000080880 | MassIVE
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