Potential role of diacylglycerol kinases in immune-mediated diseases

被引：18

作者：

Baldanzi, Gianluca ^{[1
,2
]}

Ragnoli, Beatrice ^{[3
]}

Malerba, I. Mario ^{[2
]}

机构：

[1] Ctr Translat Res Autoimmune & Allerg Dis CAAD, Biochem Grp, I-28100 Novara, Italy

[2] Univ Piemonte Orientale, Dept Translat Med, Via Solaroli 17, I-28100 Novara, Italy

[3] St Andrea Hosp, Resp Unit, I-13100 Vercelli, Italy

来源：

CLINICAL SCIENCE | 2020年 / 134卷 / 13期

关键词：

CD8(+) T-CELLS; HYPOXIC PULMONARY VASOCONSTRICTION; PERIPHERAL-BLOOD NEUTROPHILS; FMET-LEU-PHE; NF-KAPPA-B; PHOSPHATIDIC-ACID; DGK-ALPHA; NADPH OXIDASE; MULTIVESICULAR BODIES; RESPIRATORY BURST;

D O I：

10.1042/CS20200389

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The mechanism promoting exacerbated immune responses in allergy and autoimmunity as well as those blunting the immune control of cancer cells are of primary interest in medicine. Diacylglycerol kinases (DGKs) are key modulators of signal transduction, which blunt diacylglycerol (DAG) signals and produce phosphatidic acid (PA). By modulating lipid second messengers, DGK modulate the activity of downstream signaling proteins, vesicle trafficking and membrane shape. The biological role of the DGK a and. isoforms in immune cells differentiation and effector function was subjected to in deep investigations. DGK a and. resulted in negatively regulating synergistic way basal and receptor induced DAG signals in T cells as well as leukocytes. In this way, they contributed to keep under control the immune response but also downmodulate immune response against tumors. Alteration in DGK alpha activity is also implicated in the pathogenesis of genetic perturbations of the immune function such as the X-linked lymphoproliferative disease 1 and localized juvenile periodontitis. These findings suggested a participation of DGK to the pathogenetic mechanisms underlying several immune-mediated diseases and prompted several researches aiming to target DGK with pharmacologic and molecular strategies. Those findings are discussed inhere together with experimental applications in tumors as well as in other immune-mediated diseases such as asthma.

引用

页码：1637 / 1658

页数：22

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