| First Author | Takenaka N | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 1 | Pages | 202-13 |
| PubMed ID | 21182091 | Mgi Jnum | J:174654 |
| Mgi Id | MGI:5140285 | Doi | 10.1002/eji.201040675 |
| Citation | Takenaka N, et al. (2011) Overexpression of phospholipase Cepsilon in keratinocytes upregulates cytokine expression and causes dermatitis with acanthosis and T-cell infiltration. Eur J Immunol 41(1):202-13 |
| abstractText | Phospholipase Cepsilon (PLCepsilon) is an effector of Ras and Rap small GTPases. We showed previously using PLCepsilon-deficient mice that PLCepsilon plays a critical role in activation of cytokine production in non-immune skin cells in a variety of inflammatory reactions. For further investigation of its role in inflammation, we created transgenic mice overexpressing PLCepsilon in epidermal keratinocytes. The resulting transgenic mice spontaneously developed skin inflammation as characterized by formation of adherent silvery scales, excessive growth of keratinocytes, and aberrant infiltration of immune cells such as T cells and DC. Development of the skin symptoms correlated well with increased expression of factors implicated in human inflammatory skin diseases, such as IL-23, in keratinocytes, and with the accumulation of CD4(+) T cells producing IL-22, a potent inducer of keratinocyte proliferation. Intradermal injection of a blocking antibody against IL-23 as well as treatment with the immunosuppressant FK506 reversed these skin phenotypes, which was accompanied by suppression of the IL-22-producing T-cell infiltration. These results reveal a crucial role of PLCepsilon in the development of skin inflammation and suggest a mechanism in which PLCepsilon induces the production of cytokines including IL-23 from keratinocytes, leading to the activation of IL-22-producing T cells. |
