Members of the ADAMTS (A disintegrin-like and metalloproteinase with thrombospondin-1 motifs) metalloproteinase family have been shown to remodel the extracellular matrix (ECM). We have demonstrated that Adamts5-/- and Adamts7 -/-mice lose more weight, have higher lung virus titres and poor T cell immunity following influenza virus infection. In the context of our Adamts5-/- mouse model, poor immunity correlated with the accumulation of a key substrate (versican) in the MLN leading to impaired T cell migration. In conclusion, our work emphasizes the importance of ADAMTS enzyme activity in the control of influenza virus infection and highlights the potential for development of ADAMTS-based therapeutics to reduce the burden of disease.