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

Mucosal Immunol. 2020 Jul;13(4):626-636. doi: 10.1038/s41385-020-0266-x. Epub 2020 Feb 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Disease Susceptibility*
  • Gene Knockdown Techniques*
  • Gene Targeting
  • Immunity, Innate
  • Immunoglobulins / genetics*
  • Immunohistochemistry
  • Inflammation / etiology*
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Mice
  • Mice, Knockout
  • Receptors, Cytokine / genetics*
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / pathology


  • Biomarkers
  • Immunoglobulins
  • Receptors, Cytokine
  • Tslpr protein, mouse