Injury From Nematode Lung Migration Induces an IL‐13‐Dependent Hyaluronan Matrix

A consistent feature of lung injury is a rapid and sustained accumulation of hyaluronan (HA). The rodent gut-dwelling nematode <i>Nippostrongylus brasiliensis</i> (Nb) induces tissue damage as it migrates through the lungs. Type 2 immune responses are essential for the repair of the lungs, hence Nb infection is a well-established model to study immune-mediated lung repair. We found that Nb infection was associated with increased HA in the lung, which peaked at d7 post-infection (p.i.). Deposition of HA in the alveolar epithelium correlated with regions of damaged tissue and the type 2 immune response, which is characterized by eosinophilia and increased type 2 cytokines such as IL-13. Consistent with the accumulation of HA, we observed increased expression of the major synthase <i>Has2</i>, alongside decreased expression of <i>Hyal1, Hyal2</i>, and <i>Tmem2</i>, which can degrade existing HA. Expression of Tsg6 was also increased and correlated with the presence of inter-α-inhibitor heavy chain-HA complexes (HC·HA) at d7 p.i. Using IL-13-deficient mice, we found that the accumulation of HA during Nb infection was IL-13 dependent. Our data thus provide further evidence that IL-13 is a modulator of the HA matrix during lung challenge and links IL-13-mediated HA regulation to tissue repair pathways.