Early IL-10 producing B-cells and coinciding Th/Tr17 shifts during three year grass-pollen AIT

Zissler, Ulrich M.; Jakwerth, Constanze A.; Guerth, Ferdinand; Pechtold, Lisa; Aguilar-Pimentel, Juan Antonio; Dietz, Katharina; Suttner, Kathrin; Piontek, Guido; Haller, Bernhard; Hajdu, Zuzana; Schiemann, Matthias; Schmidt‐Weber, Carsten B.; Chaker, Adam

doi:10.1016/j.ebiom.2018.09.016

Cited by 65 publications

(80 citation statements)

References 54 publications

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“…On the level of secreted factors, it was shown that cytokines such as Wnt5a (Wingless-Type MMTV Integration Site Family, Member 5a) or IL-24 are expressed as response to IL-4 stimulation only, while proteins with known pathological roles such as the IL-4 induced protein CCL-26 or periostin were shown to be upregulated by IL-4 and down-regulated in IFN-γ environment. These results were consistent when comparing upper and lower airway secretions, thus confirming nasal lining fluids as a proxy for the lower respiratory tract, particularly for epithelial type-2 biomarker like CCL-26 and IL24 (308,309). The E2-related transcription factor network contained the E2 hub-transcription factors GATA3, NFE2, MEIS1, HEY2, and AHR: GATA3 is well known as the master transcription factor of type-2 response in immune cells, however it was also shown to be expressed in airway epithelial cells.…”

Section: E2-polarized Airway Epitheliumsupporting

confidence: 70%

More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

et al. 2020

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Section: E2-polarized Airway Epitheliumsupporting

confidence: 70%

More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

et al. 2020

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“…It appears that changes in the B‐cell compartment are quite restricted, as despite early reports of more global changes involving transitional and naive mature B cells in atopic dermatitis, these could not be replicated, and do not appear to be affected by AIT . The exception to this would be an increase in IL‐10‐expressing B cells, or Breg, which is associated with tolerance to bee venom and SLIT for grass pollen and HDM allergies …”

Section: Candidate Biomarkers For Immune Monitoring In Allergen Immunmentioning

confidence: 99%

“…33 The exception to this would be an increase in IL-10-expressing B cells, or Breg, which is associated with tolerance to bee venom and SLIT for grass pollen and HDM allergies. 36,128,129…”

Section: T Cellsmentioning

confidence: 99%

Recent developments and highlights in immune monitoring of allergen immunotherapy

Zelm

McKenzie

Varese

et al. 2019

Allergy

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Allergic diseases are the most common chronic immune-mediated disorders and can manifest with an enormous diversity in clinical severity and symptoms. Underlying mechanisms for the adverse immune response to allergens and its downregulation by treatment are still being revealed. As a result, there have been, and still are, major challenges in diagnosis, prediction of disease progression/evolution and treatment.Currently, the only corrective treatment available is allergen immunotherapy (AIT).AIT modifies the immune response through long-term repeated exposure to defined doses of allergen. However, as the treatment usually needs to be continued for several years to be effective, and can be accompanied by adverse reactions, many patients face difficulties completing their schedule. Long-term therapy also potentially incurs high costs. Therefore, there is a great need for objective markers to predict or to monitor individual patient's beneficial changes in immune response during therapy so that efficacy can be identified as early as possible. In this review, we specifically address recent technical developments that have generated new insights into allergic disease pathogenesis, and how these could potentially be translated into routine laboratory assays for disease monitoring during AIT that are relatively inexpensive, robust and scalable. K E Y W O R D Sallergen immunotherapy, allergy, biomarker, immune monitoring | 2343 ZELM Et aL.

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“…The understanding of the sequence of immunological events might be a prerequisite for the development of novel therapeutic strategies. Hence, in addition to the typical disease‐associated parameters, a special focus of this study was the effect of IL‐4/IL‐13 receptor inhibition on lung‐resident populations of Th2 and Treg cells at different time points of therapy, some of which are hypothesized to represent an intermediate cell population on the edge between allergen reactivity and tolerance loss …”

Section: Introductionmentioning

confidence: 99%

IL‐4 receptor α blockade prevents sensitization and alters acute and long‐lasting effects of allergen‐specific immunotherapy of murine allergic asthma

Rußkamp

Aguilar-Pimentel

Alessandrini

et al. 2019

Allergy

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Russkamp and Aguilar-Pimentel are contributed equally to this work as first authors.Abbreviations: AIT, allergen-specific immunotherapy; Alum, aluminum hydroxide magnesium hydroxide formulation; BAL, bronchoalveolar lavage; CHO, Chinese hamster ovary; FoxP3, forkhead box P3; GATA3, GATA-binding protein 3; HE, hematoxylin and eosin stain; IL-4M, IL-4 mutein, interleukin-4/interleukin-13 antagonist; i.n. AbstractBackground: Allergen-specific immunotherapy (AIT) is the only causal treatment for allergy. However, success rates vary depending on the type of allergy and disease background of the patient. Hence, strategies targeting an increased therapeutic efficacy are urgently needed. Here, the effects of blockade of IL-4 and IL-13 signaling on different phases of AIT were addressed. Methods:The impact of the recombinantly produced IL-4 and IL-13 antagonist IL-4 mutein (IL-4M) on allergic sensitization and AIT outcome in experimental allergic asthma were analyzed in a murine model. The effects of IL-4M administration were assessed prior/during sensitization, immediately after AIT under allergen challenge, and two weeks post-treatment. Results:Intervention with IL-4M prior/during sensitization led to strong induction of IgG1, IgG2a, IgG2b, and IgG3, decrease of specific and total IgE, as well as of IL-5 in serum. Similar effects on the serum immunoglobulin levels were observed immediately after IL4M-supplemented AIT during allergen challenge. Additionally, IL4M markedly suppressed type-2 cytokine secretion of splenocytes beyond the effect of AIT alone. These effects were equaled to those of AIT alone two weeks post-treatment. Intriguingly, here, IL-4M induced a sustained decrease of Th2-biased Tregs (ST2 + FOXP3 + GATA3 intermediate ).Conclusions: IL-4 and IL-13 blockade during experimental AIT demonstrates beneficial effects on immunological key parameters such as immunoglobulin and cytokine secretion immediately after AIT. Although two weeks later these effects were dropped to those of AIT alone, the number of potentially disease-triggering Th2-biased Tregs was further significantly decreased by IL-4M treatment. Hence, IL-4/IL13targeting therapies prime the immune memory in therapy success-favoring manner.

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Early IL-10 producing B-cells and coinciding Th/Tr17 shifts during three year grass-pollen AIT

Abstract: Graphical abstract

Cited by 65 publications

References 54 publications

More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

Recent developments and highlights in immune monitoring of allergen immunotherapy

IL‐4 receptor α blockade prevents sensitization and alters acute and long‐lasting effects of allergen‐specific immunotherapy of murine allergic asthma

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