The Immune‐Modulatory Role of Apolipoprotein E with Emphasis on Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Abstract

Apolipoprotein E (apoE) is a 34.2 kDa glycoprotein characterized by its wide tissue distribution and multiple functions. The nonlipid-related properties of apoE include modulating inflammation and oxidation, suppressing T cell proliferation, regulating macrophage functions, and facilitating lipid antigen presentation by CD1 molecules to natural killer T (NKT) cells, and so forth. Increasing studies have revealed that APOE ε allele might be associated with multiple sclerosis (MS), although evidence is still not sufficient enough. In this review, we summarized the current progress of the immunomodulatory functions of apoE, with special focus on the association of APOE ε allele with the clinical features of MS and of its animal model experimental autoimmune encephalomyelitis (EAE).

Granzyme B degrades extracellular matrix and contributes to delayed wound closure in apolipoprotein E knockout mice

“…Several reports have documented the suppressive effects of ApoE on inflammation. [13][14][15][16] We therefore examined wounded skin tissue from mice fed a HFD at day 16, to determine whether unresolved inflammation was present in the wounds of HFD-fed AKO mice. At day 16 Collagen and decorin levels in wounded skin.…”

“…[13][14][15][16] We therefore examined wounded skin tissue from mice fed a HFD at day 16, to determine whether unresolved inflammation was present in the wounds of HFD-fed AKO mice. At day 16 Collagen and decorin levels in wounded skin. GzmBmediated decorin degradation was found to be a potential mechanism behind collagen disorganization and accelerated skin aging in HFD-fed AKO mice.…”

“…Among those are its ability to influence inflammation. [13][14][15][16] Specifically, ApoE has been shown to suppress neutrophil and macrophage activation as well as lymphocyte proliferation. AKO mice fed a HFD for 30 weeks contained increased numbers of neutrophils in the wounded tissue compared with the young WT mice, suggesting localized inflammation in the wounds of HFD-fed AKO mice is persistent and slower to resolve, similar to chronic wounds in humans that also feature persistent neutrophil infiltration.…”

“…11,12 ApoE is expressed in multiple tissues including the skin and can also exert important immunosuppressive roles that extend beyond its role in lipid trafficking. [13][14][15][16] AKO mice are therefore susceptible to chronic inflammatory skin diseases that often increase in severity to the point where euthanasia is required. 17,18 In addition, aged AKO mice fed with a high-fat diet (HFD) exhibit skin thinning and a loss of dermal collagen density, both common features in elderly individuals who struggle with skin tearing and impaired/ chronic wound healing.…”

Association between apolipoprotein E gene polymorphism and the risk of recurrent pregnancy loss: A meta-analysis

“…Given the ethnic or geographical difference in the distribution of ApoE genotypes [13], performing population-based studies with appropriate control samples are still necessary. In addition, considering the isoform specific difference of the influence of ApoE on lipid metabolism, atherosclerosis, oxidative stress, and inflammatory and immune responses [14], RPL patients with known causes of recurrent miscarriage should not be excluded from studies that aim to identify the association between ApoE gene polymorphisms and RPL. The etiology of the E4 allele in RPL is only partly understood and may be related to lipid metabolism.…”