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IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation.
Clin Mol Allergy 2012; 10(1):8CM

Abstract

BACKGROUND

Thymic 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.

METHODS

Eosinophil 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.

RESULTS

Eosinophil 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.

CONCLUSIONS

This 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.

Authors+Show Affiliations

Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA.Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA.Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA.Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA.Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA. Department of Medicine, William S. Middleton Veterans Hospital, Madison, WI, 53705, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22838633

Citation

Cook, Ellen B., et al. "IL-3 and TNFα Increase Thymic Stromal Lymphopoietin Receptor (TSLPR) Expression On Eosinophils and Enhance TSLP-stimulated Degranulation." Clinical and Molecular Allergy : CMA, vol. 10, no. 1, 2012, p. 8.
Cook EB, Stahl JL, Schwantes EA, et al. IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation. Clin Mol Allergy. 2012;10(1):8.
Cook, E. B., Stahl, J. L., Schwantes, E. A., Fox, K. E., & Mathur, S. K. (2012). IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation. Clinical and Molecular Allergy : CMA, 10(1), p. 8. doi:10.1186/1476-7961-10-8.
Cook EB, et al. IL-3 and TNFα Increase Thymic Stromal Lymphopoietin Receptor (TSLPR) Expression On Eosinophils and Enhance TSLP-stimulated Degranulation. Clin Mol Allergy. 2012 Jul 28;10(1):8. PubMed PMID: 22838633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation. AU - Cook,Ellen B, AU - Stahl,James L, AU - Schwantes,Elizabeth A, AU - Fox,Kristen E, AU - Mathur,Sameer K, Y1 - 2012/07/28/ PY - 2012/04/20/received PY - 2012/07/28/accepted PY - 2012/7/31/entrez PY - 2012/7/31/pubmed PY - 2012/7/31/medline SP - 8 EP - 8 JF - Clinical and molecular allergy : CMA JO - Clin Mol Allergy VL - 10 IS - 1 N2 - BACKGROUND: Thymic 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. METHODS: Eosinophil 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. RESULTS: Eosinophil 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. CONCLUSIONS: This 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. SN - 1476-7961 UR - https://www.unboundmedicine.com/medline/citation/22838633/IL_3_and_TNFα_increase_Thymic_Stromal_Lymphopoietin_Receptor__TSLPR__expression_on_eosinophils_and_enhance_TSLP_stimulated_degranulation_ L2 - https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/1476-7961-10-8 DB - PRIME DP - Unbound Medicine ER -