Role of autotaxin in systemic lupus erythematosus

Yumi Tsuchida, Hirofumi Shoda, Tetsuji Sawada, Keishi Fujio, Yumi Tsuchida, Hirofumi Shoda, Tetsuji Sawada, Keishi Fujio

Abstract

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by the production of various autoantibodies and deposition of immune complexes. SLE is a heterogenous disease, and the pattern of organ involvement and response to treatment differs significantly among patients. Novel biological markers are necessary to assess the extent of organ involvement and predict treatment response in SLE. Lysophosphatidic acid is a lysophospholipid involved in various biological processes, and autotaxin (ATX), which catalyzes the production of lysophosphatidic acid in the extracellular space, has gained attention in various diseases as a potential biomarker. The concentration of ATX is increased in the serum and urine of patients with SLE and lupus nephritis. Recent evidence suggests that ATX produced by plasmacytoid dendritic cells may play an important role in the immune system and pathogenesis of SLE. Furthermore, the production of ATX is associated with type I interferons, a key cytokine in SLE pathogenesis, and ATX may be a potential biomarker and key molecule in SLE.

Keywords: SLE; autotaxin (ATX); lysophosphatidic acid; lysophospholipids; type I interferons.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2023 Tsuchida, Shoda, Sawada and Fujio.

Figures

Figure 1
Figure 1
An Overview of ATX. (A) The ATX-LPA axis: ATX is a lysophospholipase that mainly catalyzes the production of LPA from lysoglycerophospholipids, such as lysophosphatidylcholine. (LPC, lysophosphatidylcholine; ATX, autotaxin; LPA, lysophosphatidic acid; LPAR, LPA receptor). (B) Regulation of ATX expression: the expression of ATX is induced by TNF, IL-6, LPS, and type I interferons and inhibited by LPA. (TNF, tumor necrosis factor; IL-6, interleukin-6; LPS, lipopolysaccharide). (C) ATX and the pathogenesis of SLE: pDCs are activated by TLR7 and TLR9 signals, resulting in the production of type I interferons. Type I interferons induce the production of ATX and thus the production of LPA. This results in the activation of mDCs, which present autoantigens to T cells and activate them. Together, this leads to the maturation of B cells and the production of autoantibodies. Immune complexes further enhance the activation of pDCs, resulting in a positive feedback loop, contributing to the organ damage in SLE (pDC, plasmacytoid dendritic cell; TLR, toll-like receptors; mDC, myeloid dendritic cell).

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