Lipid mediators in the regulation of innate and adaptive immunity

Abstract

Life depends on lipids as the major structural components of membranes. Lipids are also crucial sources of energy in animals and humans. Fascinatingly, lipids have a diversity of additional roles in the immune system that range from acting as intercellular and intracellular signaling molecules to being modulators of membrane protein function, which influences tissue physiology in health and disease. How lipids are processed and metabolized has significant impact on cell and tissue function. In this issue of the journal, a series of reviews highlight the diverse ways lipids have been shown to serve as modulators of immunity. Murakami et al. 1 provide a comprehensive overview of secreted phospholipase A 2 (sPLA 2 ) family members, which hydrolyze phospholipids at the sn-2 position to produce lysophospholipids and fatty acids. These liberated fatty acids are often further modified to produce bioactive lipids such as eicosanoids, prostaglandins (PGs) (also see the review in this issue by Honda et al.), and leukotrienes (also see the review in this issue by Yokomizo and Shimizu) that further influence immunity in diverse manners. These phospholipid substrates are not only found in plasma membranes but also include phospholipids present in extracellular vesicles, microbial membranes, surfactants, and dietary phospholipids. The review begins with general considerations of sPLA 2 biology and then focuses on individual classical sPLA 2 families. The authors include findings from mouse models of over-expression as well as genetically engineered deficiencies in specific sPLA 2 family members, and considers the defined (and potential) physiological and pathophysiological contributions of sPLA 2 family members to immunity. Importantly, the authors address the dual positive/negative nature of many sPLA 2 activities. Beyond their roles in immunity, the authors highlight the participation of individual sPLA 2 s to pain, fertility, cardiovascular disease, cancer, and obesity, as well as providing a current account of sPLA 2 inhibitors under investigation. As such, this review will be a valuable resource for an immunological audience. The importance of PGs in inflammation is widely appreciated because of the activities of nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit the cyclooxygenase (COX) enzymes needed for PG production. However, the full details of PG and PG receptor biology are still being elucidated. In their review, Honda et al. 2 explore the broad functions of PGs and a related set of arachidonic acid derived mediators, leukotrienes (LTs), in tissue physiology and disease. They describe the enzymes involved in PG and LT synthesis, and the 13 GPCRs that they engage. The authors then provide an in-depth description of the multiple contributions of PGs and LTs to events associated with skin inflammation. This includes promoting dendritic cell (DC) migration, promoting neutrophil and eosinophil recruitment, augmenting effector T cell differentiation in draining lymph nodes, and contributing to skin-associated lym...

Lysophosphatidylserine: A Signaling Lipid with Implications in Human Diseases

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Immune Cell Migration to Cancer

“…As potent chemoattractants, LTs induce migration of neutrophils and macrophages during infection and tissue injury [315][316][317][318]. Up-to-date reviews about leukotrienes in immunity are available elsewhere [319,320]. LTs also contribute to tumorassociated inflammation, tumor growth and resistance to immunotherapy [321].…”