Mmp19, a member of the matrix metalloproteinase family, is involved in remodeling the extracellular matrix. Matrix metalloproteinases together can degrade all components of the extracellular matrix and numerous non-matrix proteins [2]. It has been associated with various biological processes and diseases, and gene-targeted mouse models have been crucial in understanding its functions.

In a mouse model of contact hypersensitivity, MMP19-deficient mice showed impaired T cell-mediated immune reaction, with limited inflammatory cell influx, low keratinocyte proliferation, and reduced activated CD8(+) T cells in draining lymph nodes. In the thymus, thymocytes had low proliferation rates and an augmented number of CD4(+)CD8(+) double-positive cells, suggesting MMP19 is important for T cell development and cutaneous immune responses [3].

In the context of pulmonary fibrosis, MMP19 expression was increased in the lung endothelial cells of IPF patients and bleomycin-induced mice. MMP19-AAV-infected mice showed that MMP19 promoted endothelial-to-mesenchymal transition (E(nd)MT), increased endothelial barrier permeability, stimulated monocyte infiltration, and aggravated pulmonary fibrosis. Blocking its interacting proteins SDF1 and ET1 alleviated the fibrosis, indicating MMP19 promotes E(nd)MT via interaction with ET1 and monocyte infiltration via the SDF1/CXCR4 axis [1].

In conclusion, Mmp19 is essential for T cell development and cutaneous immune responses, and plays a significant role in pulmonary fibrosis through promoting E(nd)MT and monocyte infiltration. The study of Mmp19 using gene-targeted mouse models has provided valuable insights into its functions in these specific biological processes and disease conditions.