Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis.
BACKGROUND
Atopic 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 in cellular and humoral response in AD, but accumulating evidence has shown that follicular helper T cell (TFH), a critical player in humoral immunity, is associated with disease severity and plays an important role in AD pathogenesis.


OBJECTIVES
This study aimed at investigating how TFHs are generated during the pathogenesis of AD, particularly what is the role of keratinocyte-derived cytokine TSLP and Langerhans cells (LCs).


METHODS
Two experimental AD mouse models were employed: (1) triggered by the overproduction of TSLP through topical application of MC903, and (2) induced by epicutaneous allergen ovalbumin (OVA) sensitization.


RESULTS
This study demonstrated that the development of TFHs and germinal center (GC) response were crucially dependent on TSLP in both the MC903 model and the OVA sensitization model. Moreover, we found that LCs promoted TFH differentiation and GC response in the MC903 model, and the depletion of Langerin+ dendritic cells (DCs) or selective depletion of LCs diminished the TFH/GC response. By contrast, in the model with OVA sensitization, LCs inhibited TFH/GC response and suppressed TH2 skin inflammation and the subsequent asthma. Transcriptomic analysis of Langerin+ and Langerin- migratory DCs revealed that Langerin+ DCs became activated in the MC903 model, whereas these cells remained inactivated in OVA sensitization model.


CONCLUSIONS
Together, these studies revealed a dual functionality of LCs in TSLP-promoted TFH and TH2 differentiation in AD pathogenesis.
['Marschall|Pierre|P|', 'Wei|Ruicheng|R|', 'Segaud|Justine|J|', 'Yao|Wenjin|W|', 'Hener|Pierre|P|', 'German|Beatriz Falcon|BF|', 'Meyer|Pierre|P|', 'Hugel|Cecile|C|', 'Ada Da Silva|Grace|G|', 'Braun|Reinhard|R|', 'Kaplan|Daniel H|DH|', 'Li|Mei|M|']
D000485:Allergens D000818:Animals D002117:Calcitriol D002454:Cell Differentiation D016207:Cytokines D003876:Dermatitis, Atopic D003879:Dermatologic Agents D020869:Gene Expression Profiling D007801:Langerhans Cells D008807:Mice, Inbred BALB C D008822:Mice, Transgenic D010047:Ovalbumin D012867:Skin D006377:T-Lymphocytes, Helper-Inducer
Langerhans cells mouse Atopic dermatitis TSLP dendritic cells T(FH) T(H)2 allergen sensitization