Title | Targeted deletion of the TSLP receptor reveals cellular mechanisms that promote type 2 airway inflammation. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Kabata H, Flamar A-L, Mahlakõiv T, Moriyama S, Rodewald H-R, Ziegler SF, Artis D |
Journal | Mucosal Immunol |
Volume | 13 |
Issue | 4 |
Pagination | 626-636 |
Date Published | 2020 07 |
ISSN | 1935-3456 |
Keywords | Adaptive Immunity, Animals, Biomarkers, CD4-Positive T-Lymphocytes, Dendritic Cells, Disease Models, Animal, Disease Susceptibility, Gene Knockdown Techniques, Gene Targeting, Immunity, Innate, Immunoglobulins, Immunohistochemistry, Inflammation, Mice, Mice, Knockout, Receptors, Cytokine, Respiratory Mucosa |
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. |
DOI | 10.1038/s41385-020-0266-x |
Alternate Journal | Mucosal Immunol |
PubMed ID | 32066836 |
PubMed Central ID | PMC7311324 |
Grant List | R01 AI074878 / AI / NIAID NIH HHS / United States R01 AI095466 / AI / NIAID NIH HHS / United States R01 AI102942 / AI / NIAID NIH HHS / United States U19 AI125378 / AI / NIAID NIH HHS / United States U01 AI095608 / AI / NIAID NIH HHS / United States |