Abstract
BackgroundThymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Therefore, we sought to determine whether TSLP could activate eosinophils, focusing on measuring the regulation of TSLPR expression on eosinophils and degranulation in response to TSLP, as well as other eosinophil activation responses.MethodsEosinophil mRNA expression of TSLPR and IL-7Rα was examined by real-time quantitative PCR of human eosinophils treated with TNFα and IL-5 family cytokines, and TSLPR surface expression on eosinophils was analyzed by flow cytometry. Eosinophils were stimulated with TSLP (with and without pre-activation with TNFα and IL-3) and evaluated for release of eosinophil derived neurotoxin (EDN), phosphorylation of STAT5, and survival by trypan blue exclusion. A blocking antibody for TSLPR was used to confirm the specificity of TSLP mediated signaling on eosinophil degranulation.ResultsEosinophil expression of cell surface TSLPR and TSLPR mRNA was upregulated by stimulation with TNFα and IL-3. TSLP stimulation resulted in release of EDN, phosphorylation of STAT5 as well as promotion of viability and survival. TSLP-stimulated eosinophil degranulation was inhibited by a functional blocking antibody to TSLPR. Pre-activation of eosinophils with TNFα and IL-3 promoted eosinophil degranulation at lower concentrations of TSLP stimulation.ConclusionsThis study demonstrates that eosinophils are activated by TSLP and that eosinophil degranulation in response to TSLP may be enhanced on exposure to cytokines present in allergic inflammation, indicating that the eosinophil has the capacity to participate in TSLP-driven allergic responses.
Highlights
Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation
We demonstrate that activation of eosinophils with cytokines present in allergic inflammation (TNFα and IL-3) upregulate Thymic stromal lymphopoietin receptor (TSLPR) gene expression in a dose dependent manner
TSLP activation of eosinophils Given the role of eosinophil granule proteins in the pathophysiology of allergic diseases, we investigated the ability of TSLP to promote eosinophil degranulation
Summary
Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine which plays a key role in allergic diseases such as asthma, atopic dermatitis, allergic rhinitis, nasal polyposis, and chronic allergic keratoconjunctivis [1,2,3,4,5]. TSLP is a member of the hematopoietic cytokine family that includes a number of cytokines important in allergic disease including IL-2, IL-4, IL-7, and IL-13. Regulation of TSLPR expression in these cells has not been well studied In allergic diseases, these TSLPR-expressing cells exist in a milieu of pro-allergic and pro-inflammatory cytokines and other factors (e.g., allergens, bacterial products, lipid mediators) that have the potential to modulate expression of the TSLPR, yet the biological consequences of enhanced expression have not been well examined [13]
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