Monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals (the deposition of which leads to gout and CPP disease, respectively) induce macrophages to release IL-1β via activation of the NLRP3 inflammasome, which results in joint inflammation. A new study elucidates a role for cell volume regulation, and for osmo-sensitive LRRC8 anion channels in particular, in MSU crystal- and CPP crystal-induced inflammation.

Previous work had shown that hypotonic challenge and subsequent regulatory volume decrease (RVD) can induce NLRP3 inflammasome activation in macrophages, and that macrophages that phagocytose crystals have altered intracellular osmolarity, cell swelling and water content. The identification of LRRC8 as a regulator of cell volume led the researchers to explore its role in NLRP3 inflammasome activation after crystal exposure.