Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis

BackgroundAtopic dermatitis (AD) is among the most common chronic inflammatory skin diseases, usually occurring early in life, and often preceding other atopic diseases such as asthma. TH2 has been believed to play a crucial role cellular humoral response AD, but accumulating evidence shown that follicular helper T cell (TFH), critical player immunity, associated with disease severity plays an important AD pathogenesis.ObjectivesThis study aimed at investigating how TFHs are generated during pathogenesis of particularly what keratinocyte-derived cytokine TSLP Langerhans cells (LCs).MethodsTwo experimental mouse models were employed: (1) triggered by overproduction through topical application MC903, (2) induced epicutaneous allergen ovalbumin (OVA) sensitization.ResultsThis demonstrated development germinal center (GC) crucially dependent on both MC903 model OVA sensitization model. Moreover, we found LCs promoted TFH differentiation GC model, depletion Langerin+ dendritic (DCs) or selective diminished TFH/GC response. By contrast, sensitization, inhibited suppressed inflammation subsequent Transcriptomic analysis Langerin− migratory DCs revealed became activated whereas these remained inactivated model.ConclusionsTogether, studies dual functionality TSLP-promoted pathogenesis. Atopic This (LCs). Two sensitization. Together,