期刊
NATURE IMMUNOLOGY
卷 22, 期 2, 页码 154-U78出版社
NATURE PORTFOLIO
DOI: 10.1038/s41590-020-00844-7
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资金
- National Institutes of Health [AI119015, AI135528]
- Agencia Nacional de Promocion Cientifica y Tecnologica
- Federal Ministry of Education and Research, Germany [01EO1502]
- Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany's Excellence Strategy [EXC 2051, 390713860]
- Fundacion Sales
- Fundacion Bunge y Born
Studies have identified galectin-1 as a new DAMP that promotes inflammation by inhibiting CD45. The release of galectin-1 during cytosolic LPS sensing is detrimental and affects endotoxin shock.
Damage-associated molecular patterns (DAMPs) are released during necrotic cell death and contribute to driving inflammation. Rathinam and colleagues show that galectin-1 is a new DAMP that functions by inhibiting the receptor phosphatase CD45. Inflammatory caspase sensing of cytosolic lipopolysaccharide (LPS) triggers pyroptosis and the concurrent release of damage-associated molecular patterns (DAMPs). Collectively, DAMPs are key determinants that shape the aftermath of inflammatory cell death. However, the identity and function of the individual DAMPs released are poorly defined. Our proteomics study revealed that cytosolic LPS sensing triggered the release of galectin-1, a beta-galactoside-binding lectin. Galectin-1 release is a common feature of inflammatory cell death, including necroptosis. In vivo studies using galectin-1-deficient mice, recombinant galectin-1 and galectin-1-neutralizing antibody showed that galectin-1 promotes inflammation and plays a detrimental role in LPS-induced lethality. Mechanistically, galectin-1 inhibition of CD45 (Ptprc) underlies its unfavorable role in endotoxin shock. Finally, we found increased galectin-1 in sera from human patients with sepsis. Overall, we uncovered galectin-1 as a bona fide DAMP released as a consequence of cytosolic LPS sensing, identifying a new outcome of inflammatory cell death.
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