Ablation of Siglec-E augments brain inflammation and ischemic injury.

Autor: Li L; Department of Pharmaceutical Sciences, Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA., Chen Y; Department of Pharmaceutical Sciences, Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA., Sluter MN; Department of Pharmaceutical Sciences, Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA., Hou R; Department of Pharmaceutical Sciences, Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA., Hao J; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA., Wu Y; Children's Foundation Research Institute at Le Bonheur Children's Hospital, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA., Chen GY; Children's Foundation Research Institute at Le Bonheur Children's Hospital, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA., Yu Y; Department of Pharmaceutical Sciences, Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA., Jiang J; Department of Pharmaceutical Sciences, Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA. jjiang18@uthsc.edu.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2022 Jul 20; Vol. 19 (1), pp. 191. Date of Electronic Publication: 2022 Jul 20.
DOI: 10.1186/s12974-022-02556-1
Abstrakt: Sialic acid immunoglobulin-like lectin E (Siglec-E) is a subtype of pattern recognition receptors found on the surface of myeloid cells and functions as a key immunosuppressive checkpoint molecule. The engagement between Siglec-E and the ligand α 2,8 -linked disialyl glycans activates the immunoreceptor tyrosine-based inhibitory motif (ITIM) in its intracellular domain, mitigating the potential risk of autoimmunity amid innate immune attacks on parasites, bacteria, and carcinoma. Recent studies suggest that Siglec-E is also expressed in the CNS, particularly microglia, the brain-resident immune cells. However, the functions of Siglec-E in brain inflammation and injuries under many neurological conditions largely remain elusive. In this study, we first revealed an anti-inflammatory role for Siglec-E in lipopolysaccharide (LPS)-triggered microglial activation. We then found that Siglec-E was induced within the brain by systemic treatment with LPS in mice in a dose-dependent manner, while its ablation exacerbated hippocampal reactive microgliosis in LPS-treated animals. The genetic deficiency of Siglec-E also aggravated oxygen-glucose deprivation (OGD)-induced neuronal death in mouse primary cortical cultures containing both neurons and glial cells. Moreover, Siglec-E expression in ipsilateral brain tissues was substantially induced following middle cerebral artery occlusion (MCAO). Lastly, the neurological deficits and brain infarcts were augmented in Siglec-E knockout mice after moderate MCAO when compared to wild-type animals. Collectively, our findings suggest that the endogenous inducible Siglec-E plays crucial anti-inflammatory and neuroprotective roles following ischemic stroke, and thus might underlie an intrinsic mechanism of resolution of inflammation and self-repair in the brain.
(© 2022. The Author(s).)
Databáze: MEDLINE
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