Targeted deletion of the TSLP receptor reveals cellular mechanisms that promote type 2 airway inflammation

Hiroki Kabata, Anne Laure Flamar, Tanel Mahlakõiv, Saya Moriyama, Hans Reimer Rodewald, Steven F. Ziegler, David Artis

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Thymic stromal lymphopoietin (TSLP) is a critical upstream cytokine inducing type 2 inflammation in various diseases, including asthma and atopic dermatitis. Accumulating evidence suggests that TSLP can directly stimulate a variety of immune cells, such as dendritic cells (DCs), basophils, T cells, and group 2 innate lymphoid cells (ILC2s). However, which cell types directly respond to TSLP in vivo and how TSLP initiates type 2 inflammation has remained controversial. To define the precise role of TSLP in vivo, for the first time we generated multiple cell lineage-specific TSLP receptor-deficient mice to systematically dissect the cell-intrinsic requirements for TSLP responsiveness in type 2 inflammation in the lung. In papain-induced innate immune-mediated type 2 airway inflammation, TSLP directly stimulated ILC2s, but not basophils, leading to enhanced type 2 inflammation. On the other hand, in OVA-induced adaptive immune-mediated type 2 airway inflammation, TSLP principally acted on DCs and CD4 + T cells during the sensitization phase, but not basophils or ILC2s, and facilitated the development of Th2 cell-mediated airway inflammation. Together, these findings reveal that TSLP activates distinct immune cell cascades in the context of innate and adaptive immune-mediated type 2 inflammation.

Original languageEnglish
Pages (from-to)626-636
Number of pages11
JournalMucosal Immunology
Volume13
Issue number4
DOIs
Publication statusPublished - 2020 Jul 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Kabata, H., Flamar, A. L., Mahlakõiv, T., Moriyama, S., Rodewald, H. R., Ziegler, S. F., & Artis, D. (2020). Targeted deletion of the TSLP receptor reveals cellular mechanisms that promote type 2 airway inflammation. Mucosal Immunology, 13(4), 626-636. https://doi.org/10.1038/s41385-020-0266-x