Characterization of inflammation and fibrosis in the NIF.CD2-GFP mouse model

Fibrosis is a process characterized by the accumulation of extracellular matrix components and is attributed to excessive scar formation and is a common feature of many chronic inflammatory conditions. Fibrogenesis involves multiple inflammatory cells including NKT cells, which have been suggested to play a prominent role in the control of this process. Here we characterize a transgenic mouse model for chronic inflammation and fibrosis, in which the green fluorescent protein (GFP) reporter gene is expressed in transgenic NKT cells under the CD2-promotor. Using flow cytometry analysis and immunohistochemical characterization of the NIF.CD2-GFP mouse we found the expression of the CD2-GFP marker to be specific for NKT cells and NK cells amongst liver leukocytes. The inflammatory phenotype in the liver was associated with extensive myeloid infiltration, accompanied by hepatic stellate cell activation and fibrotic scarring primarily localized around the vessels. Further, we showed by adoptive transfer that GFP-expressing NKT cells localize to the liver, maintain GFP expression of high intensity and could potentially drive the development of inflammation and fibrosis in these mice. Based on these findings, we conclude that this novel mouse model enables us to track transgenic NKT cells and study the progression of chronic inflammation and fibrosis in more detail and specifically, the functional properties of NKT cells and the mechanisms by which they act in disease development. (Less)