IHPV16 E7 expression in skin induces TSLP secretion, type 2 ILC in filtration and atopic dermatitis-like lesions

JuAnne-Sophie Bergot, Nastasia Monnet, Son Le Tran, Deepak Mittal, Jane Al-Kouba, Raymond J Steptoe, Michele A Grimbaldeston, Ian H Frazer and James W Wells.

Nature. Immunology & Cell biology. 1-8. 2015.

Speaker: Wei-Lin Chen (陳薇稜)                     Time: 13:10~14:00, Jun. 6, 2015

Commentator: Yee-Shin Lin (林以行 老師)            Room: Room 601

Abstract:

Atopic dermatitis (AD) is a chronic inflammatory and relapsing eczema in the skin. The histological and immunological features about AD are hyperkeratosis, acanthoisis and spongiosis in skin tissue. Clinical signs of AD indicate that epithelial cells express high level thymic stromal lymphopoietin (TSLP), which signaling could prime dendritic cells (DCs) to secret proinflammatory cytokines and trigger the circulative IgE production and T_H2-dependent immune response. Proinflammatory cytokine could recruit immune cells to infiltrate into skin, such as skin-homing T cells, mast cells (MCs), DCs and innate lymphoid cells (ILCs). Recently, accumulating evidences have indicated that innate lymphoid cell 2 (ILC2) involves in the AD pathological process. ^[2] ILC2 arerecruited by interlukin-33 (IL-33), the cytokines were produced by epithelial cell. However, etiologic factors about AD is still unknown. Fortunately, author found there are similar symptoms between AD and human papillomavirus (HPV) infection, both of them have increasing TSLP production in epithelial cell.^[1]  According to previous study, HPV 16 oncoprotein E7 have expressed in the keratinocytes under K14 promoter could cause squamous epithelial hyperplasia.^[3]  In addition to that author used K14.E7 transgenic mice (E7 mice) to investigate etiological and disease process of AD. The authors found E7 mice could spontaneously develop clinical and pathological symptoms of AD. Next, they also demonstrated E7 mice were susceptibility to atopic march process with extrinsic challenged by allergen. In the immunological function of E7 mice, which developed with ILC2-dependent pathological process, but not within IL-33, MCs or T cells-dependent manner.Overall, the authors investigated that HPV 16 K14.E7 might be the pivotal causative agent of AD and susceptibility to hypersensitivity reaction.

References:

1.  Feng Q, et al. 2012. Th2 type in flammation promotes the gradual progression of HPV-infected cervical cells to cervical carcinoma. Gynecol Oncol. 127: 412 –419.

2.  Roediger B, et al. 2013. Cutaneous immunosurveillance and regulation of in flammation by group 2 innate lymphoid cells. Nat Immunol. 14: 564 –573.

3.  Herber R, et al. Squamous epithelial hyperplasia and carcinoma in mice transgenic for the human papillomavirus type 16 E7 oncogene. J Virol. 1996; 70: 1873–1881.