| First Author | Andrianne M | Year | 2017 |
| Journal | JCI Insight | Volume | 2 |
| Issue | 11 | PubMed ID | 28570274 |
| Mgi Jnum | J:287969 | Mgi Id | MGI:6407631 |
| Doi | 10.1172/jci.insight.92979 | Citation | Andrianne M, et al. (2017) Tristetraprolin expression by keratinocytes controls local and systemic inflammation. JCI Insight 2(11) |
| abstractText | Tristetraprolin (TTP, encoded by the Zfp36 gene) regulates the mRNA stability of several important cytokines. Due to the critical role of this RNA-binding protein in the control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL23 by myeloid cells, such as macrophages or DCs. Here, we generated mice with conditional deletion of TTP in keratinocytes (Zfp36fl/flK14-Cre mice, referred to herein as Zfp36DeltaEP mice). Unlike DC-restricted (CD11c-Cre) or myeloid cell-restricted (LysM-Cre) TTP ablation, these mice developed exacerbated inflammation in the imiquimod-induced psoriasis model. Furthermore, Zfp36DeltaEP mice progressively developed a spontaneous pathology with systemic inflammation, psoriatic-like skin lesions, and dactylitis. Finally, we provide evidence that keratinocyte-derived TNF production drives these different pathological features. In summary, these findings expand current views on the initiation of psoriasis and related arthritis by revealing the keratinocyte-intrinsic role of TTP. |
