Disruption of macrophage cell volume drives inflammatory responses and type I interferon signalling

This experiment explored the impact of cell volume increase and regulatory volume decrease (RVD) on the transcriptome of mouse macrophages. Bone marrow-derived macrophages (BMDMs) were isolated from CX3CR1-cre LRRC8A-flox, or littermate wild-type (CX3CR1-cre negative, LRRC8A flox) mice (PMID: 33216713), or Cre control (CX3CR1-cre positive, no LRRC8A flox) and incubated in DMEM (D6429, Sigma) (Isotonic, 310 mOsm/kg) or 50% H2O (Hypotonic, 170 mOsm/kg) for 4 hours. Following hypotonic stimulation, wild-type BMDMs undergo cell swelling and RVD whereas LRRC8A knockout BMDMs fail to undergo RVD and remain swollen.