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Article ; Online: Type 2-polarized memory B cells hold allergen-specific IgE memory.

Koenig, Joshua F E / Knudsen, Niels Peter H / Phelps, Allyssa / Bruton, Kelly / Hoof, Ilka / Lund, Gitte / Libera, Danielle Della / Lund, Anders / Christensen, Lars Harder / Glass, David R / Walker, Tina D / Fang, Allison / Waserman, Susan / Jordana, Manel / Andersen, Peter S

Science translational medicine

2024 Volume 16, Issue 733, Page(s) eadi0944

Abstract: Allergen-specific immunoglobulin E (IgE) antibodies mediate pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. Here, we ...

Abstract	Allergen-specific immunoglobulin E (IgE) antibodies mediate pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. Here, we report a population of type 2-polarized MBCs defined as CD23
MeSH term(s)	Humans ; Rhinitis, Allergic, Seasonal/metabolism ; Memory B Cells ; Allergens ; Immunoglobulin E ; Rhinitis, Allergic ; Immunoglobulin G ; Food Hypersensitivity
Chemical Substances	Allergens ; Immunoglobulin E (37341-29-0) ; Immunoglobulin G
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.adi0944
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Article ; Online: Production and use of antigen tetramers to study antigen-specific B cells.

Phelps, Allyssa / Pazos-Castro, Diego / Urselli, Francesca / Grydziuszko, Emily / Mann-Delany, Olivia / Fang, Allison / Walker, Tina D / Guruge, Rangana Talpe / Tome-Amat, Jaime / Diaz-Perales, Araceli / Waserman, Susan / Boonyaratanakornkit, Jim / Jordana, Manel / Taylor, Justin J / Koenig, Joshua F E

Nature protocols

2024 Volume 19, Issue 3, Page(s) 727–751

Abstract: B cells generate antibodies that provide protection from infection, but also cause pathology in autoimmune and allergic conditions. Antigen-specific B cells can be detected by binding their surface antibody receptors with native antigens conjugated to ... ...

Abstract	B cells generate antibodies that provide protection from infection, but also cause pathology in autoimmune and allergic conditions. Antigen-specific B cells can be detected by binding their surface antibody receptors with native antigens conjugated to fluorescent probes, a technique that has revealed substantial insight into B cell activation and function. This protocol describes the process of generating fluorescent antigen tetramer probes and delineates a process of enriching large samples based on antigen-specificity for high-resolution analyses of the antigen-specific B cell repertoire. Enrichment of tetramer-binding cells allows for detection of antigen-specific B cells as rare as 1 in 100 million cells, providing sufficient resolution to study naive B cells and IgE-expressing cells by flow cytometry. The generation of antigen tetramers involves antigen biotinylation, assessment of biotin:antigen ratio for optimal tetramer loading and polymerization around a streptavidin-fluorophore backbone. We also describe the construction of a control tetramer to exclude B cells binding to the tetramer backbone. We provide a framework to validate whether tetramer probes are detecting true antigen-specific B cells and discuss considerations for experimental design. This protocol can be performed by researchers trained in basic biomedical/immunological research techniques, using instrumentation commonly found in most laboratories. Constructing the antigen and control tetramers takes 9 h, though their specificity should be assessed before experimentation and may take weeks to months depending on the method of validation. Sample enrichment requires ~2 h but is generally time and cost neutral as fewer cells are run through the flow cytometer.
MeSH term(s)	Antigens ; B-Lymphocytes ; Flow Cytometry/methods
Chemical Substances	Antigens
Language	English
Publishing date	2024-01-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2244966-8
ISSN	1750-2799 ; 1754-2189
ISSN (online)	1750-2799
ISSN	1754-2189
DOI	10.1038/s41596-023-00930-8
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Article ; Online: Reply to "Be smart in choosing antihistamines".

Chu, Derek K / Freitag, Tosha / Marrin, Andrea / Walker, Tina D / Avilla, Ernie / Freitag, Andreas / Spill, Paul / Foster, Gary A / Thabane, Lehana / Jordana, Manel / Waserman, Susan

The journal of allergy and clinical immunology. In practice

2023 Volume 11, Issue 4, Page(s) 1332–1333

MeSH term(s)	Humans ; Histamine Antagonists/therapeutic use ; Histamine H1 Antagonists
Chemical Substances	Histamine Antagonists ; Histamine H1 Antagonists
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2023.01.047
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Article ; Online: Peanut Oral Immunotherapy With or Without H

Chu, Derek K / Freitag, Tosha / Marrin, Andrea / Walker, Tina D / Avilla, Ernie / Freitag, Andeas / Spill, Paul / Foster, Gary A / Thabane, Lehana / Jordana, Manel / Waserman, Susan

The journal of allergy and clinical immunology. In practice

2022 Volume 10, Issue 9, Page(s) 2386–2394

Abstract: Background: Current forms of peanut oral immunotherapy (OIT) are associated with side effects, and there is a lack of evidence addressing how to mitigate them.: Objective: To determine whether premedication with desloratadine and ranitidine results ... ...

Abstract	Background: Current forms of peanut oral immunotherapy (OIT) are associated with side effects, and there is a lack of evidence addressing how to mitigate them. Objective: To determine whether premedication with desloratadine and ranitidine results in fewer side effects during peanut OIT/desensitization. Methods: A total of 43 patients with peanut allergy (mean age, 7.6 ± 2.1 years, 37% females, 63% males, baseline eliciting dose, 33 ± 26 mg) were randomized to OIT with or without concomitant H Results: Adverse reactions occurred more in the OIT groups compared with the double-placebo group (OIT with antihistamines vs double-placebo hazard ratio, 3.75 [95% CI, 2.79-4.72]; OIT with placebo antihistamines vs double-placebo, hazard ratio, 4.62 [95% CI, 3.61-5.62]). Patients given antihistamines cotreatment with OIT had a similar risk of adverse events compared with those who did not use antihistamines with OIT (hazard ratio, 1.23 [95% CI, 0.49-1.97]). OIT with and without antihistamines accelerated the incidence rate of adverse events compared with double-placebo (4.8 and 6.4 events per patient vs 3.5 per patient, incidence rate ratio, 2.49 [95% CI, 1.36-4.56] and 2.04 [95% CI, 1.01-4.15], respectively). Antihistamines pretreatment modestly reduced the frequency of moderate to severe adverse reactions among OIT-treated groups (1.9 per patient vs 4.2 per patient, incidence rate ratio, 0.46 [95% CI, 0.24-0.89]), primarily urticaria (0.6 vs 2.1 per patient) followed by abdominal pain (2.6 vs 4.2 per patient), but increased neuropsychiatric adverse events (primarily tiredness and sedation, 2.3 vs 0.7 per patient). Eliciting doses after treatment were similar in all groups. Quality of life improved similarly regardless of treatment with peanut OIT or placebo OIT. Conclusions: Peanut OIT with antihistamines modestly reduce the skin and gastrointestinal components of the high incidence of adverse reactions during OIT, and there are no clear differences in improvement in quality of life whether treated with OIT, OIT with antihistamines, or placebo OIT despite OIT being effective in inducing desensitization. Safer food allergy treatment approaches that importantly improve quality of life need to be proved in future robust randomized trials.
MeSH term(s)	Administration, Oral ; Allergens/therapeutic use ; Animals ; Arachis ; Child ; Child, Preschool ; Desensitization, Immunologic/methods ; Female ; Fishes ; Histamine Antagonists ; Histamine H1 Antagonists/therapeutic use ; Humans ; Immunologic Factors ; Male ; Peanut Hypersensitivity/therapy ; Premedication ; Quality of Life
Chemical Substances	Allergens ; Histamine Antagonists ; Histamine H1 Antagonists ; Immunologic Factors
Language	English
Publishing date	2022-05-25
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2022.05.015
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Article ; Online: Identifying Falls Risk Screenings Not Documented with Administrative Codes Using Natural Language Processing.

Zhu, Vivienne J / Walker, Tina D / Warren, Robert W / Jenny, Peggy B / Meystre, Stephane / Lenert, Leslie A

AMIA ... Annual Symposium proceedings. AMIA Symposium

2018 Volume 2017, Page(s) 1923–1930

Abstract: Quality reporting that relies on coded administrative data alone may not completely and accurately depict providers' performance. To assess this concern with a test case, we developed and evaluated a natural language processing (NLP) approach to identify ...

Abstract	Quality reporting that relies on coded administrative data alone may not completely and accurately depict providers' performance. To assess this concern with a test case, we developed and evaluated a natural language processing (NLP) approach to identify falls risk screenings documented in clinical notes of patients without coded falls risk screening data. Extracting information from 1,558 clinical notes (mainly progress notes) from 144 eligible patients, we generated a lexicon of 38 keywords relevant to falls risk screening, 26 terms for pre-negation, and 35 terms for post-negation. The NLP algorithm identified 62 (out of the 144) patients who falls risk screening documented only in clinical notes and not coded. Manual review confirmed 59 patients as true positives and 77 patients as true negatives. Our NLP approach scored 0.92 for precision, 0.95 for recall, and 0.93 for F-measure. These results support the concept of utilizing NLP to enhance healthcare quality reporting.
MeSH term(s)	Accidental Falls ; Algorithms ; Clinical Coding ; Electronic Health Records ; Humans ; Information Storage and Retrieval/methods ; Mass Screening ; Natural Language Processing ; Risk Assessment/methods
Language	English
Publishing date	2018-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1942-597X
ISSN (online)	1942-597X
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Article ; Online: Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity.

Jiménez-Saiz, Rodrigo / Anipindi, Varun C / Galipeau, Heather / Ellenbogen, Yosef / Chaudhary, Roopali / Koenig, Joshua F / Gordon, Melissa E / Walker, Tina D / Mandur, Talveer S / Abed, Soumeya / Humbles, Alison / Chu, Derek K / Erjefält, Jonas / Ask, Kjetil / Verdú, Elena F / Jordana, Manel

Frontiers in immunology

2020 Volume 11, Page(s) 155

Abstract: Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the ... ...

Abstract	Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This was associated with changes in the production of enteric signals that regulate eosinophil attraction and survival, and was fully reversed by complex colonization. Additionally, SI eosinophils of GF mice exhibited more cytoplasmic protrusions and less granule content than SPF controls. Lastly, we generated a novel strain of eosinophil-deficient GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as compared to GF controls. Overall, our study demonstrates that commensal microbes regulate intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization to food antigens. These data support a critical interplay between the commensal microbiota and intestinal eosinophils in shaping homeostatic, innate, and adaptive immune processes in health and disease.
MeSH term(s)	Animals ; Disease Models, Animal ; Eosinophilia ; Eosinophils/immunology ; Female ; Food Hypersensitivity/blood ; Food Hypersensitivity/immunology ; Food Hypersensitivity/microbiology ; Gastrointestinal Microbiome/immunology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/microbiology ; Intestine, Small/immunology ; Intestine, Small/microbiology ; Leukocyte Count ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Specific Pathogen-Free Organisms ; Th2 Cells/immunology
Language	English
Publishing date	2020-02-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00155
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Article ; Online: Interrupting reactivation of immunologic memory diverts the allergic response and prevents anaphylaxis.

Bruton, Kelly / Spill, Paul / Vohra, Shabana / Baribeau, Owen / Manzoor, Saba / Gadkar, Siyon / Davidson, Malcolm / Walker, Tina D / Koenig, Joshua F E / Ellenbogen, Yosef / Florescu, Alexandra / Wen, Jianping / Chu, Derek K / Waserman, Susan / Jiménez-Saiz, Rodrigo / Epelman, Slava / Robbins, Clinton / Jordana, Manel

The Journal of allergy and clinical immunology

2020 Volume 147, Issue 4, Page(s) 1381–1392

Abstract: Background: IgE production against innocuous food antigens can result in anaphylaxis, a severe life-threatening consequence of allergic reactions. The maintenance of IgE immunity is primarily facilitated by IgG: Objective: Our aim was to investigate ... ...

Abstract	Background: IgE production against innocuous food antigens can result in anaphylaxis, a severe life-threatening consequence of allergic reactions. The maintenance of IgE immunity is primarily facilitated by IgG Objective: Our aim was to investigate the critical requirements for an IgE recall response in peanut allergy. Methods: We used a novel human PBMC culture platform, a mouse model of peanut allergy, and various experimental readouts to assess the IgE recall response in the presence and absence of IL-4Rα blockade. Results: In human PBMCs, we have demonstrated that blockade of IL-4/IL-13 signaling aborted IgE production after activation of a recall response and skewed the cytokine response away from a dominant type 2 signature. T Conclusion: The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.
MeSH term(s)	Anaphylaxis/immunology ; Animals ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/immunology ; Disease Models, Animal ; Female ; Humans ; Immunoglobulin E/immunology ; Immunologic Memory ; Leukocytes, Mononuclear/immunology ; Mice, Inbred C57BL ; Peanut Hypersensitivity/immunology ; Receptors, Interleukin-4/immunology ; Mice
Chemical Substances	Cytokines ; Receptors, Interleukin-4 ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2020-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2020.11.042
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Article ; Online: Lifelong memory responses perpetuate humoral T

Jiménez-Saiz, Rodrigo / Chu, Derek K / Mandur, Talveer S / Walker, Tina D / Gordon, Melissa E / Chaudhary, Roopali / Koenig, Joshua / Saliba, Sarah / Galipeau, Heather J / Utley, Adam / King, Irah L / Lee, Kelvin / Ettinger, Rachel / Waserman, Susan / Kolbeck, Roland / Jordana, Manel

The Journal of allergy and clinical immunology

2017 Volume 140, Issue 6, Page(s) 1604–1615.e5

Abstract: Background: A number of food allergies (eg, fish, shellfish, and nuts) are lifelong, without any disease-transforming therapies, and unclear in their underlying immunology. Clinical manifestations of food allergy are largely mediated by IgE. Although ... ...

Abstract	Background: A number of food allergies (eg, fish, shellfish, and nuts) are lifelong, without any disease-transforming therapies, and unclear in their underlying immunology. Clinical manifestations of food allergy are largely mediated by IgE. Although persistent IgE titers have been attributed conventionally to long-lived IgE Objective: We sought to evaluate mechanisms underlying persistent IgE and allergic responses to food allergens. Methods: We used a model of peanut allergy and anaphylaxis, various knockout mice, adoptive transfer experiments, and in vitro assays to identify mechanisms underlying persistent IgE humoral immunity over almost the entire lifespan of the mouse (18-20 months). Results: Contrary to conventional paradigms, our data show that clinically relevant lifelong IgE titers are not sustained by long-lived IgE Conclusions: These findings can explain lifelong food allergies observed in human subjects as the consequence of allergen exposures that recurrently activate memory B cells and identify these as a therapeutic target with disease-transforming potential.
MeSH term(s)	Allergens/immunology ; Anaphylaxis/immunology ; Animals ; Arachis/immunology ; B-Lymphocyte Subsets/immunology ; B-Lymphocytes/immunology ; Cells, Cultured ; Food Hypersensitivity/immunology ; Humans ; Immunity, Humoral ; Immunoglobulin E/metabolism ; Immunologic Memory ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Th2 Cells/immunology
Chemical Substances	Allergens ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2017-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2017.01.018
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Article: Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma.

Chu, Derek K / Al-Garawi, Amal / Llop-Guevara, Alba / Pillai, Regina A / Radford, Katherine / Shen, Pamela / Walker, Tina D / Goncharova, Susanna / Calhoun, William J / Nair, Parameswaran / Jordana, Manel

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology

2015 Volume 11, Issue 1, Page(s) 14

Abstract: Background: Determining the cellular and molecular phenotypes of inflammation in asthma can identify patient populations that may best benefit from targeted therapies. Although elevated IL-6 and polymorphisms in IL-6 signalling are associated with lung ... ...

Abstract	Background: Determining the cellular and molecular phenotypes of inflammation in asthma can identify patient populations that may best benefit from targeted therapies. Although elevated IL-6 and polymorphisms in IL-6 signalling are associated with lung dysfunction in asthma, it remains unknown if elevated IL-6 levels are associated with a specific cellular inflammatory phenotype, and how IL-6 blockade might impact such inflammatory responses. Methods: Patients undergoing exacerbations of asthma were phenotyped according to their airway inflammatory characteristics (normal cell count, eosinophilic, neutrophilic, mixed granulocytic), sputum cytokine profiles, and lung function. Mice were exposed to the common allergen, house dust-mite (HDM), in the presence or absence of endogenous IL-6. The intensity and nature of lung inflammation, and levels of pro-granulocytic cytokines and chemokines under these conditions were analyzed. Results: Elevated IL-6 was associated with a lower FEV1 in patients with mixed eosinophilic-neutrophilic bronchitis. In mice, allergen exposure increased lung IL-6 and IL-6 was produced by dendritic cells and alveolar macrophages. Loss-of-function of IL-6 signalling (knockout or antibody-mediated neutralization) abrogated elevations of eosinophil and neutrophil recruiting cytokines/chemokines and allergen-induced airway inflammation in mice. Conclusions: We demonstrate the association of pleiotropic cellular airway inflammation with IL-6 using human and animal data. These data suggest that exacerbations of asthma, particularly those with a combined eosinophilic and neutrophilic bronchitis, may respond to therapies targeting the IL-6 pathway and therefore, provide a rational basis for initiation of clinical trials to evaluate this.
Language	English
Publishing date	2015-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2434973-2
ISSN	1710-1492 ; 1710-1484
ISSN (online)	1710-1492
ISSN	1710-1484
DOI	10.1186/s13223-015-0081-1
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Article: IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization

Chu, Derek K / Llop-Guevara, Alba / Walker, Tina D / Flader, Kristin / Goncharova, Susanna / Boudreau, Jeanette E / Moore, Cheryl Lynn / In, Tracy Seunghyun / Waserman, Susan / Coyle, Anthony J / Kolbeck, Roland / Humbles, Alison A / Jordana, Manel

The Journal of Allergy and Clinical Immunology. 2013 Jan., v. 131, no. 1

2013

Abstract: BACKGROUND: Allergen exposure at lung and gut mucosae can lead to aberrant TH2 immunity and allergic disease. The epithelium-associated cytokines thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 are suggested to be important for the initiation of ... ...

Abstract	BACKGROUND: Allergen exposure at lung and gut mucosae can lead to aberrant TH2 immunity and allergic disease. The epithelium-associated cytokines thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 are suggested to be important for the initiation of these responses. OBJECTIVE: We sought to investigate the contributions of TSLP, IL-25, and IL-33 in the development of allergic disease to the common allergens house dust mite (HDM) or peanut. METHODS: Neutralizing antibodies or mice deficient in TSLP, IL-25, or IL-33 signaling were exposed to HDM intranasally or peanut intragastrically, and immune inflammatory and physiologic responses were evaluated. In vitro assays were performed to examine specific dendritic cell (DC) functions. RESULTS: We showed that experimental HDM-induced allergic asthma and food allergy and anaphylaxis to peanut were associated with TSLP production but developed independently of TSLP, likely because these allergens functionally mimicked TSLP inhibition of IL-12 production and induction of OX40 ligand (OX40L) on DCs. Blockade of OX40L significantly lessened allergic responses to HDM or peanut. Although IL-25 and IL-33 induced OX40L on DCs in vitro, only IL-33 signaling was necessary for intact allergic immunity, likely because of its superior ability to induce DC OX40L and expand innate lymphoid cells in vivo. CONCLUSION: These data identify a nonredundant, IL-33–driven mechanism initiating TH2 responses to the clinically relevant allergens HDM and peanut. Our findings, along with those in infectious and transgenic/surrogate allergen systems, favor a paradigm whereby multiple molecular pathways can initiate TH2 immunity, which has implications for the conceptualization and manipulation of these responses in health and disease.
Keywords	allergens ; anaphylaxis ; asthma ; digestive system ; dust ; dust mites ; food allergies ; genetically modified organisms ; immunity ; in vitro studies ; interleukin-12 ; mice ; mucosa ; neutralizing antibodies ; peanuts
Language	English
Dates of publication	2013-01
Size	p. 187-200.e8.
Publishing place	Mosby, Inc.
Document type	Article
ZDB-ID	121011-7
ISSN	1085-8725 ; 1097-6825 ; 0091-6749
ISSN (online)	1085-8725 ; 1097-6825
ISSN	0091-6749
DOI	10.1016/j.jaci.2012.08.002
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