TSLP and IL-33 reciprocally promote each other's lung protein expression and ILC2 receptor expression to enhance innate type-2 airway inflammation

Shinji Toki, Kasia Goleniewska, Jian Zhang, Weisong Zhou, Dawn C. Newcomb, Baohua Zhou, Hirohito Kita, Kelli L. Boyd, Ray S. Peebles

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: The epithelial cell-derived danger signal mediators thymic stromal lymphopoietin (TSLP) and IL-33 are consistently associated with adaptive Th2 immune responses in asthma. In addition, TSLP and IL-33 synergistically promoted group 2 innate lymphoid cell (ILC2) activation to induce innate allergic inflammation. However, the mechanism of this synergistic ILC2 activation is unknown. Methods: BALB/c WT and TSLP receptor-deficient (TSLPR−/−) mice were challenged intranasally with Alternaria extract (Alt-Ext) or PBS for 4 consecutive days to evaluate innate airway allergic inflammation. WT mice pre-administered with rTSLP or vehicle, TSLPR−/− mice, and IL-33 receptor-deficient (ST2−/−) mice were challenged intranasally with Alt-Ext or vehicle once or twice to evaluate IL-33 release and TSLP expression in the lung. TSLPR and ST2 expression on lung ILC2 were measured by flow cytometry after treatment of rTSLP, rIL-33, rTSLP + rIL-33, or vehicle. Results: Thymic stromal lymphopoietin receptor deficient mice had significantly decreased the number of lung ILC2 expressing IL-5 and IL-13 following Alt-Ext-challenge compared to WT mice. Further, eosinophilia, protein level of lung IL-4, IL-5, and IL-13, and airway mucus score were also significantly decreased in TSLPR−/− mice compared to WT mice. Endogenous and exogenous TSLP increased Alt-Ext-induced IL-33 release into BALF, and ST2 deficiency decreased Alt-Ext-induced TSLP expression in the lung. Further, rTSLP and rIL-33 treatment reciprocally increased each other's receptor expression on lung ILC2 in vivo and in vitro. Conclusion: Thymic stromal lymphopoietin and IL-33 signaling reciprocally enhanced each other's protein release and expression in the lung following Alt-Ext-challenge and each other's receptor expression on lung ILC2 to enhance ILC2 activation.

Original languageEnglish (US)
Pages (from-to)1606-1617
Number of pages12
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume75
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • Alternaria-extract (Alt-Ext)
  • Group 2 innate lymphoid cells (ILC2)
  • IL-33
  • TSLP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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