| First Author | Perry JSA | Year | 2019 |
| Journal | Nat Cell Biol | Volume | 21 |
| Issue | 12 | Pages | 1532-1543 |
| PubMed ID | 31792382 | Mgi Jnum | J:282848 |
| Mgi Id | MGI:6384038 | Doi | 10.1038/s41556-019-0431-1 |
| Citation | Perry JSA, et al. (2019) Interpreting an apoptotic corpse as anti-inflammatory involves a chloride sensing pathway. Nat Cell Biol 21(12):1532-1543 |
| abstractText | Apoptotic cell clearance (efferocytosis) elicits an anti-inflammatory response by phagocytes, but the mechanisms that underlie this response are still being defined. Here, we uncover a chloride-sensing signalling pathway that controls both the phagocyte 'appetite' and its anti-inflammatory response. Efferocytosis transcriptionally altered the genes that encode the solute carrier (SLC) proteins SLC12A2 and SLC12A4. Interfering with SLC12A2 expression or function resulted in a significant increase in apoptotic corpse uptake per phagocyte, whereas the loss of SLC12A4 inhibited corpse uptake. In SLC12A2-deficient phagocytes, the canonical anti-inflammatory program was replaced by pro-inflammatory and oxidative-stress-associated gene programs. This 'switch' to pro-inflammatory sensing of apoptotic cells resulted from the disruption of the chloride-sensing pathway (and not due to corpse overload or poor degradation), including the chloride-sensing kinases WNK1, OSR1 and SPAK-which function upstream of SLC12A2-had a similar effect on efferocytosis. Collectively, the WNK1-OSR1-SPAK-SLC12A2/SLC12A4 chloride-sensing pathway and chloride flux in phagocytes are key modifiers of the manner in which phagocytes interpret the engulfed apoptotic corpse. |
