Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling

Nakajima S., et al. J Allergy Clin Immunol. 2012;129(4):1048–55.

Speaker：Yu-Pu Hsia (夏雨璞)                                    Time：15:10~16:00, March 27, 2013

Commentator: Dr. Shun-Hua Chen (陳舜華老師)       Place：Room 601

Abstract:

Skin plays an important immunologic role in immune responses to foreign allergens. The common disease of skin allergy is atopic dermatitis (AD). AD is an allergic inflammatory disease caused by the interaction between skin barrier damage and allergic skin inflammation. Langerhans cells (LCs) are one type of immature dendritic cell that resides in the epidermis of skin and are the first APCs to contact with allergens. LCs were thought to play an critical role in the development of atopic dermatitis [1]. Previous study indicated that activation of keratinocytes produced thymic stromallymphopoietin (TSLP) to induce Th2-type response through the TSLP receptor (TSLPR) in AD [2]. Because TSLP is highly expressed in the proximity of LCs, the authors hypothesized that LCs play an essential role in epicutaneous sensitization with protein antigens through TSLP signaling. To test this hypothesis, authors established the AD model induced by epicutaneous sensitization with ovalbumin (OVA) in LC-depleted and TSLPR-deficient mice. Firstly, they found that LC- depleted mice demonstrated impaired OVA-induced skin inflammation and decreased OVA-specific IgElevels. Furthermore, T-cell proliferation and Th2-type responses were decreased in LC depleted mice. These data indicated that LCs are crucial for AD development. Because TSLPR on LCs is upregulated by OVA sensitization, they generated mice in which TSLPRs were lacking in LCs. After OVA sensitization, TSLPR-deficient mice had milder clinical and histologic features than wild-type mice. Consistently, OVA-specific IgE levels and Th2 immune response were significantly lower in TSLPR-deficient mice. These data indicated that TSLPRs on LCs are dispensable for antigen-specific T-cell proliferation but necessary for Th2 induction. In conclusion, LCs initiated epicutaneous sensitization with protein allergens and induced AD development through TSLP signaling.

References:

1. Elentner A, et al. Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice. J Cell Mol Med. 2009;13(8B):2658-72
2. Kitajima M, et al. TSLP enhances the function of helper type 2 cells. Eur J Immunol. 2011;41(7):1862-71.