Allergies – A T cells perspective in the era beyond the TH1/TH2 paradigm

Berker, Moritz; Frank, Larissa; Geßner, Anja Lidwina; Graßl, Niklas; Holtermann, Anne Verena; Höppner, Stefanie; Kraef, Christian; Leclaire, Martin Dominik; Maier, Pia; Messerer, David Alexander Christian; Möhrmann, Lino; Nieke, Jan Philipp; Schoch, Diana; Soll, Dominik; Woopen, Christina

doi:10.1016/j.clim.2016.11.001

Cited by 52 publications

(40 citation statements)

References 160 publications

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“…Allergic asthma is a type I immediate-hypersensitivity reaction, characterized by an augmented Th2 response and an attenuated Th1 response [6,30,31]. Since abundant Th2 cytokines contribute to disease, therapeutic treatment that reduces the Th2 response and increases the Th1 response may be beneficial.…”

Section: Discussionmentioning

confidence: 99%

“…Reduced exposure to microorganisms during these vulnerable periods contributes to the development of lymphocytes with a T helper 2 (Th2) phenotype, i.e., lymphocytes known to promote asthmatic symptoms by producing Th2 cytokines, along with the induced accumulation of leukocytes. Th2 lymphocytes reduce the numbers and function of Th1 lymphocytes, and this reduction in the nonallergic Th1 lymphocyte subset predisposes to allergic-type diseases such as asthma [6,7].…”

mentioning

confidence: 99%

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Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Huang²,

Zhu

et al. 2018

Int Arch Allergy Immunol

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Background: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. Methods: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. Results: TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1 (Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam₃CSK₄. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. Conclusions: This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Huang²,

Zhu

et al. 2018

Int Arch Allergy Immunol

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“…Interferon (IFN)‐γ, IL‐2, IL‐4, IL‐5, IL‐9 and IL‐13 production was used to explore activation of TCs . Supernatants were collected after 72 hours of co‐culture, and stored at −80°C until analysis by cytometric bead array (CBA).…”

Section: Methodsmentioning

confidence: 99%

“…Interferon (IFN)-γ, IL-2, IL-4, IL-5, IL-9 and IL-13 production was used to explore activation of TCs. [32][33][34][35] Supernatants were collected after 72 hours of co-culture, and stored at −80 C until analysis by cytometric bead array (CBA). BD CBA mouse IFN-γ, IL-2, IL-4, IL-5, IL-9 and IL-13 Flex Sets (BD Biosciences, San Jose, California) were used to quantify the amount of cytokine secreted in the supernatant, according to the manufacturer's instructions.…”

Section: Cytokine Releasementioning

confidence: 99%

Activation of T cells by dendritic cells exposed to a reference sensitizer: Towards a promising model to assess the allergenic potential of chemicals

et al. 2018

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“…In atopic dermatitis on the contrary, innate and specific immune defense arms accelerate acute toward chronic inflammation linked with a mixed Th1/Th17/Th2 immune response [5] (Fig. 1d, e).…”

Section: Atopic Dermatitis Modelsmentioning

confidence: 99%

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

Jensen‐Jarolim

Pali‐Schöll

Roth‐Walter

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewAnimal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases.Recent findingsAllergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment.SummaryIn atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles.

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Allergies – A T cells perspective in the era beyond the TH1/TH2 paradigm

Cited by 52 publications

References 160 publications

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Activation of T cells by dendritic cells exposed to a reference sensitizer: Towards a promising model to assess the allergenic potential of chemicals

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

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