Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects up to 20% of children and 3-5% of adults worldwide. AD typically presents an aberrant type 2 immune response, shown by skin infiltration of T helper 2 (Th2) cells, eosinophils and basophils, accompanied Tfh cell response and an elevation of blood immunoglobulin E levels. The keratinocyte-derived cytokine TSLP has been recognized to play a key role in AD pathogenesis, but how TSLP signals through its receptor (TSLPR) expressed on dendritic cells (DCs) to drive T cell response remain to be investigated. 
 
Methods: We used a TSLP overexpression-induced AD model originally established in the lab. We employed DC-selective knock-out mouse lines and gene reporter mouse tools, combined with flow cytometry and single cell transcriptomic analyses, and DC-T cell coculture to investigate TSLP-driven T cell response. 
 
Results: We showed TSLP-TSLPR signaling in DCs not only induces Th2 but also regulatory T cells (Treg). We found that TSLP-activated DCs upregulated their expression of the costimulatory molecule OX40L, thus took use of our newly generated OX40L knockout mice to characterize the implication of OX40L from DC in Th2/Treg responses, as well as OX40L-reporter mice to identify these DCs from surface marker expression to transcriptomic profiles. 
 
Conclusions: Our results provide insights on how skin TSLP signals through DCs to drive different T cell responses.
 
Acknowledgement: We would like to acknowledge the funding supports from l’Agence Nationale de la Recherche (ANR-19-CE17-0017; ANR-19-CE17-0021; ANR-22-CE14-0023)