Immune regulation of the hyaluronan matrix in the lung during infection, injury and repair

The extracellular matrix component hyaluronan (HA) is an enormous polysaccharide that dictates tissue elasticity, hydration and directs immune cell behaviour. During lung inflammation, HA content increases dramatically and it becomes modified by HA-binding proteins to form diverse HA matrix structures. While HA matrix formation is essential for effective tissue repair, it is a key component of the remodelled airway in asthma and a driver of disease severity in influenza and COVID-19. We recently discovered that the type 2 cytokine IL-13 induces HA in the lung during acute viral infection, chronic allergic airway remodelling and during repair following nematode migration. Critically, we do not fully understand the composition of the HA matrix in these distinct settings and how or when it helps resolve inflammation, repair damage or promote disease pathology. Using established disease models, we will study IL-13-mediated HA matrix formation and function with the aim to: 1) define the composition and spatially map the HA matrix in pathogenic vs protective contexts; 2) define the immune context that instructs HA matrix formation; 3) manipulate the HA matrix to address its impact on the immune response and disease outcome for therapeutic benefit. Keywords: Hyaluronan; extracellular-matrix; IL-13; macrophage; asthma; helminth infection; respiratory virus.