The immunological function of CD52 and its targeting in organ transplantation
INFLAMMATION RESEARCH
Authors: Zhao, Yang; Su, Huiting; Shen, Xiaofei; Du, Junfeng; Zhang, Xiaodong; Zhao, Yong
Abstract
CD52 (Campath-1 antigen), a glycoprotein of 12 amino acids anchored to glycosylphosphatidylinositol, is widely expressed on the cell surface of immune cells, such as mature lymphocytes, natural killer cells (NK), eosinophils, neutrophils, monocytes/macrophages, and dendritic cells (DCs). The anti-CD52 mAb, alemtuzumab, was used widely in clinics for the treatment of patients such as organ transplantation. In the present manuscript, we will briefly summarize the immunological function of CD52 and discuss the application of anti-CD52 mAb in transplantation settings. We reviewed studies published until July 2016 to explore the role of CD52 in immune cell function and its implication in organ transplantation. We showed that ligation of cell surface CD52 molecules may offer costimulatory signals for T-cell activation and proliferation. However, soluble CD52 molecules will interact with the inhibitory sialic acid-binding immunoglobulin-like lectin 10 (Siglec10) to significantly inhibit T cell proliferation and activation. Although the physiological and pathological significances of CD52 molecules are still poorly understood, the anti-CD52 mAb, alemtuzumab, was used widely for the treatment of patients with chronic lymphocytic leukemia, autoimmune diseases as well as cell and organ transplantation in clinics. Studies clearly showed that CD52 can modulate T-cell activation either by its intracellular signal pathways or by the interaction of soluble CD52 and Siglec-10 expressing on T cells. However, the regulatory functions of CD52 on other immune cell subpopulations in organ transplantation require to be studied in the near future.
Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Authors: Ponsuksili, Siriluck; Murani, Eduard; Trakooljul, Nares; Schwerin, Manfred; Wimmers, Klaus
Abstract
Biochemical and biophysical processes that take place in muscle under relaxed and stressed conditions depend on the abundance and activity of gene products of metabolic and structural pathways. In livestock at post-mortem, these muscle properties determine aspects of meat quality and are measurable. The conversion of muscle to meat mimics pathological processes associated with muscle ischemia, injury or damage in humans and it is an economic factor in pork production. Linkage, association, and expression analyses independently contributed to the identification of trait-associated molecular pathways and genes. We aim at providing multiple evidences for the role of specific genes in meat quality by integrating a genome-wide association study (GWAS) for meat quality traits and the detection of eQTL based on trait-correlated expressed genes and trait-associated markers. The GWAS revealed 51 and 200 SNPs significantly associated with meat quality in a crossbred Pietrain Chi(German Landrace Chi Large White) (Pi Chi(GL Chi LW)) and a purebred German Landrace (GL) population, respectively. Most significant SNPs in Pi Chi(GL Chi LW) were located on chromosomes (SSC) 4 and 6. The data of 47,836 eQTLs at a significance level of p < 10(-5) were used to scale down the number candidate genes located in these regions. These SNPs on SSC4 showed association with expression levels of ZNF704, IMPA1, and OXSR1; SSC6 SNPs were associated with expression of SIGLEC10 and PIH1D1. Most significant SNPs in GL were located on SSC6 and associated with expression levels of PIH1D1, SIGLEC10, TBCB, LOC100518735, KIF1B, LOC100514845, and two unknown genes. The abundance of transcripts of these genes in muscle, in turn, is significantly correlated with meat quality traits. We identified several genes with evidence for their candidacy for meat quality arising from the integrative approach of a genome-wide association study and eQTL analysis.