T cells

The Metzincins are a superfamily of zinc-dependent endopeptidases associated with the regulation of the extracellular matrix (ECM). Their members include A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs), A Disintegrin and Metalloproteinases (ADAMs), and the matrix metalloproteinases (MMPs). Metzincins exhibit diverse functions associated with both physiological and pathological states that include the proteolytic degradation of the ECM, regulation of various growth factors, cell surface receptors, and chemokines, and mediation of biological functions such as extravasation, survival, and proliferation. In pathological conditions such as cancer associated with chronic inflammation and multiple sclerosis associated with neurodegeneration, dysregulation of Metzincin activities are a hallmark of disease progression and severity. Hence, Metzincins are therapeutic targets for various disease states and research into optimal Metzincin inhibitor design is an ongoing exploit.

The thymus provides a unique microenvironment that facilitates T lymphocytes differentiation and maturation. However, the thymus atrophies after puberty which leads to an overall expression of metabolism gene pathways and low gene expression of certain peroxide scavenger enzymes such as catalase in thymic stromal compartments. From this data, we postulate that thymic stromal cells are highly susceptible to oxidative damage. We utilized a transgenic mice model overexpressing human catalase targeted to the mitochondria (mCat) to test our hypothesis that gerater oxidative protection should lower the degree of thymus atrophy. Our experiment focused on a direct comparison of organ weights (thymus, kidney, lymph nodes, spleen and heart), cellularity and histology between transgenic and wildtype mice. We found that mCat had selective increases in thymus size.