Siglecs are predominantly expressed by cells of the immune system and can be divided into two main groups according to sequence homology and conservation. One group comprises the Siglecs that are conserved across mammals, whereas the other (known as the CD33rSiglec family) consists of the Siglecs that vary greatly between different species in terms of gene number and sequence. As CD33rSiglecs have been shown to deliver inhibitory signals to immune cells, the authors questioned whether their anti-inflammatory activities may correlate with mammalian lifespans. Indeed, when they assessed 14 mammalian species, they found a strong positive correlation between the number of CD33rSiglec family genes and the maximum lifespan of a species.
To examine whether the CD33rSiglecs were contributing to longevity, the authors used mice lacking Siglec-E. This receptor is expressed by neutrophils and tissue macrophages and is the predominant CD33rSiglec in mice. Compared with wild-type littermates, Siglec-E-deficient mice had markedly reduced survival over a period of 100 weeks and showed increased greying and thinning of the epidermis. They also showed poorer performance in tests designed to measure learning and spatial memory. The Siglec-E-deficient mice did not show any evidence of chronic systemic inflammation and had similar leukocyte counts to wild-type controls. However, Siglec-E-deficient mice showed sporadic development of inflammatory tissue foci in the liver, kidneys and lungs.
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