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TSLP drives acute TH2-cell differentiation in lungs
Jen-Feng Lai1, Lucas J Thompson1, Steven F Ziegler1
1Benaroya Research Institute at Virginia Mason, Seattle, Wash.
The Journal of Allergy and Clinical Immunology
|April 19, 2020
Summary
Thymic stromal lymphopoietin (TSLP) directly promotes T helper 2 (TH2) cell differentiation in the lungs. CD11c-expressing interstitial macrophages (IMs) are key drivers of TSLP-mediated allergic airway inflammation.
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine crucial for type 2 inflammatory responses.
- Elevated TSLP levels are observed in human asthma, and it promotes type 2 airway inflammation in mice, but mechanisms are unclear.
Purpose of the Study:
- To elucidate the mechanistic role of TSLP in type 2 airway inflammation.
- To identify cellular players involved in TSLP-mediated immune responses in the airways.
Main Methods:
- Mice were treated with TSLP and antigen to assess immune responses.
- Flow cytometry analyzed airway cellular responses.
- Conditional TSLP receptor deletion and adoptive transfer identified key cell subsets.
Main Results:
- TSLP directly induced TH2 cell differentiation in the lung, independent of lymph nodes.
- CD11c-expressing interstitial macrophages (IMs) were identified as necessary and sufficient for TSLP-mediated TH2 cell differentiation and airway inflammation.
- Ablation of CD11c-expressing IMs or their TSLP receptor signaling attenuated TH2 cell-driven eosinophilia.
Conclusions:
- TSLP and CD11c-expressing IMs play a novel mechanistic role in acute TH2 cell-dependent allergic airway inflammation.
- This study reveals a new function for TSLP in directly promoting type 2 responses within the lung.
