Review
The roles of autotaxin/lysophosphatidic acid in immune regulation and asthma

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Abstract

Lysophosphatidic acid (LPA) species are present in almost all organ systems and play diverse roles through its receptors. Asthma is an airway disease characterized by chronic allergic inflammation where various innate and adaptive immune cells participate in establishing Th2 immune response. Here, we will review the contribution of LPA and its receptors to the functions of immune cells that play a key role in establishing allergic airway inflammation and aggravation of allergic asthma.

Section snippets

Overview of autotaxin/LPA pathway

Lysophosphatidic acid (LPA), a membrane derived from glycerophospholipid, is present in most biological fluids like plasma, urine, bronchoalveolar fluid (BALF), saliva, cerebrospinal fluid, and tissue extracts [[1], [2], [3], [4]]. Depending on their difference in length and saturation degree, LPA species can be subdivided into saturated (C16:0 and C18:0), monounsaturated (C18:1), and polyunsaturated (C18:2, C20:4, C22:5, and C22:6) forms [[4], [5], [6]]. As a smallest water-soluble bioactive

ATX/LPA as immunological modifiers

In the normal process of wound repair and tissue remodeling, ATX/LPA mediates platelet aggregation, cytokine production, and cellular migration and proliferation of immune cells, fibroblasts, endothelial cells, and keratinocytes [41]. However, in the unresolved chronic pathological conditions like rheumatoid arthritis, asthma, lung fibrosis, liver cirrhosis, chronic colitis, and the malignancies related with inflammation, aberrantly activated ATX/LPA signals aggravate chronic inflammation

The role of ATX/LPA in asthma

In the normal healthy state, a constitutive ATX expression is found in airway epithelial cells and alveolar macrophages, and the secreted ATX and its byproducts, LPA species, are also detected in BAL fluids [2,24,108] However, the normal phenotypes with no pathologic lung defect seen in multiple ATX transgenic mice, including whole body ATX deficient (Enpp2+/−, Rosa26Cre-ERT2/Enpp2fl/fl [1,40], airway epithelial cell-specific ATX deleted (CC10Enpp2−/−), and ATX overexpressed transgenic mice

Future direction

Asthma is a complex immunologic airway disease where various types of immune cells are intertwined to establish a chronic Th2 allergic immune response. Intercellular communication between immune cells in the milieu of airways and lungs is an integral part of asthma pathogenesis. Locally produced LPA plays a key role in cellular communication through its binding to six different receptors that immune cells express variably during the course of the disease process. The local concentration of LPA

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by NIH grant R01 HL126852.

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