<scp>GARP</scp> inhibits allergic airway inflammation in a humanized mouse model

Meyer-Martin, Helen; Hahn, Susanne A.; Beckert, Hendrik; Belz, Christina; Heinz, Andreas; Jonuleit, Helmut; Becker, Christian; Taube, Christian; Korn, Stephanie; Buhl, Roland; Reuter, Sebastian; Tuettenberg, Andrea

doi:10.1111/all.12883

Cited by 19 publications

(18 citation statements)

References 29 publications

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“…Many studies addressed predictors of remission or persistence of asthma from early childhood through adulthood (23)(24)(25)(26). Immunoregulatory parameters related to the outcome of childhood asthma have been widely discussed, however are not yet well established (4,7,10,19,27). Speci c observations in the present study, regarding immunology parameters, were surprising.…”

Section: Discussioncontrasting

confidence: 58%

“…Glycoprotein A repetitions predominant (GARP) has strong anti-in ammatory and regulatory effects on human cells in vitro as well as in vivo. It is involved in the regulation of peripheral tolerance (10) and plays an essential role in mediating suppressive effects of Treg (10Authors showed that sGARP had a synergistic effect together with Treg by preventing in ammation (10). In our study we showed higher expression of GARP positive cells in patients without AR.…”

Section: Discussionsupporting

confidence: 58%

“…The expression of suppressor of cytokine signaling 3 (SOCS3) is induced by various cytokines, including IL6, IL10, and interferon (IFN)gamma (8,9). Glycoprotein A repetitions predominant (GARP) is involved in the regulation of peripheral tolerance (10). Our hypothesis was that some cells' mediators might play more prominent role in these processes than others.…”

Section: Introductionmentioning

confidence: 99%

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Allergic rhinitis and house dust mite sensitization determine persistence of asthma in children.

Brzozowska

Woicka-Kolejwa

Jerzyńska

et al. 2020

Preprint

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Background: MAS study revealed that chronic course of asthma characterised by airway hyper-responsiveness and impairment of lung function at school age is determined by continuing allergic airway inflammation which begin in the first 3 years of life. Respiratory tract infections early in life, childhood allergic comorbidities, exposure to environmental determinants of asthma and active smoking may all contribute to increased risk of allergic disorders. While these correlations have been established, there is little understanding of the immunological mechanisms by which asthma develops into a persistent disease, or by which symptoms regress. Methods: Eighty patients were included into the analysis. Clinical and immunoregulatory predictors of asthma were analyzed. Results: Presence of mAPI criteria as well as the presence of house dust mite-allergy and allergic rhinitis at present, were associated with a reduced prevalence of asthma remission. The presence of increased eosinophil blood count in API (Asthma Predictive Index) criteria was associated with a lower expression of CD25 positive cells. Current presence of HDM-allergy was associated with a higher FeNO level and higher expression of CD25CD71 positive cells. Allergic rhinitis was associated with a higher expression of PPAR and CD25CD71 positive cells; in the same group of patients a lower expression of GARP positive cells were observed. Conclusions: Probability of persistence of childhood asthma was largely determined by the presence of allergic rhinitis and sensitization to HDM. Our results suggest natural remission of clinical symptoms of asthma in children are not fully related to immunoregulation processes. Additionally, API criteria are related to asthma persistence.

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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Allergic rhinitis and house dust mite sensitization determine persistence of asthma in children.

Brzozowska

Woicka-Kolejwa

Jerzyńska

et al. 2020

Preprint

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“…Recent work on GARP in the context of TGF-β has attempted to address the role of GARP in promoting a tolerogenic environment (6,(34)(35)(36). However, no study has addressed the physiologic role of GARP in tolerance in vivo.…”

Section: Introductionmentioning

confidence: 99%

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

Wallace¹,

Wu²,

Salem³

et al. 2018

JCI Insight

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“…Also transfer models were employed, in which human blood immune cells stimulated in-vitro with allergens are transferred to immune-deficient mice to mimic human asthma [38]. …”

Section: Introductionmentioning

confidence: 99%

Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis

Jensen‐Jarolim

Pali‐Schöll

Roth‐Walter

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewAnimal models published within the past 18 months on asthma, food allergy and anaphylaxis, all conditions of rising public health concern, were reviewed.Recent findingsWhile domestic animals spontaneously develop asthma, food allergy and anaphylaxis, in animal models, divergent sensitization and challenge routes, dosages, intervals and antigens are used to induce asthmatic, food allergic or anaphylactic phenotypes. This must be considered in the interpretation of results. Instead of model antigens, gradually relevant allergens such as house dust mite in asthma, and food allergens like peanut, apple and peach in food allergy research were used. Novel engineered mouse models such as a mouse with a T-cell receptor for house dust mite allergen Der p 1, or with transgenic human hFcγR genes, facilitated the investigation of single molecules of interest. Whole-body plethysmography has become a state-of-the-art in-vivo readout in asthma research. In food allergy and anaphylaxis research, novel techniques were developed allowing real-time monitoring of in-vivo effects following allergen challenge. Networks to share tissues were established as an effort to reduce animal experiments in allergy which cannot be replaced by in-vitro measures.SummaryNatural and artificial animal models were used to explore the pathophysiology of asthma, food allergy and anaphylaxis and to improve prophylactic and therapeutic measures. Especially the novel mouse models mimicking molecular aspects of the complex immune network in asthma, food allergy and anaphylaxis will facilitate proof-of-concept studies under controlled conditions.

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GARP inhibits allergic airway inflammation in a humanized mouse model

Abstract: Induction of peripheral tolerance via sGARP is a promising potential approach to treat allergic airway diseases.

Cited by 19 publications

References 29 publications

Allergic rhinitis and house dust mite sensitization determine persistence of asthma in children.

Allergic rhinitis and house dust mite sensitization determine persistence of asthma in children.

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis

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