TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation - Université Toulouse III - Paul Sabatier - Toulouse INP Accéder directement au contenu
Article Dans Une Revue Journal of Experimental Medicine Année : 2024

TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation

Pauline Schmitt
Anais Duval
Cécile Dedieu
Emilie Mirey
Corinne Cayrol

Résumé

Epithelium-derived cytokines or alarmins, such as interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), are major players in type 2 immunity and asthma. Here, we demonstrate that TNF-like ligand 1A (TL1A) is an epithelial alarmin, constitutively expressed in alveolar epithelium at steady state in both mice and humans, which cooperates with IL-33 for early induction of IL-9high ILC2s during the initiation of allergic airway inflammation. Upon synergistic activation by IL-33 and TL1A, lung ILC2s acquire a transient IL-9highGATA3low “ILC9” phenotype and produce prodigious amounts of IL-9. A combination of large-scale proteomic analyses, lung intravital microscopy, and adoptive transfer of ILC9 cells revealed that high IL-9 expression distinguishes a multicytokine-producing state-of-activated ILC2s with an increased capacity to initiate IL-5-dependent allergic airway inflammation. Similar to IL-33 and TSLP, TL1A is expressed in airway basal cells in healthy and asthmatic human lungs. Together, these results indicate that TL1A is an epithelium-derived cytokine and an important cofactor of IL-33 in the airways.

Domaines

Immunologie
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Dates et versions

hal-04605493 , version 1 (11-06-2024)

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Pauline Schmitt, Anais Duval, Mylène Camus, Emma Lefrançais, Stéphane Roga, et al.. TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation. Journal of Experimental Medicine, 2024, 221 (6), ⟨10.1084/jem.20231236⟩. ⟨hal-04605493⟩
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