The Role of Endogenous Eicosapentaenoic Acid and Docosahexaenoic Acid-Derived Resolvins in Systemic Sclerosis

Figure 1. The acute inflammatory response and potential fates for the acute inflammatory process. Tissue damage induced by endogenous or exogenous stimuli leads to the generation of acute inflammatory responses, including various types of proinflammatory cell infiltrations and the production of plenty of proinflammatory mediators. Polymorphonuclear leukocytes infiltration especially neutrophils induce the influx of monocyte-derived macrophages to remove apoptotic cells and debris. Throughout the resolution phase of inflammation, resolvins (Rvs) promote the efferocytosis of macrophages and differentiation of proinflammatory macrophages (MΦ) into anti-inflammatory macrophages. At the post-resolution phase of inflammation, adaptive immunity response (B and T cells) establishes which contributes the wound healing. Any dysregulation of these processes may lead to chronic inflammation and fibrosis. Rvs limit the acute inflammatory process, thus, they prevent the development of chronic inflammation and fibrosis.

Figure 2. The anti-inflammatory, pro-resolution, and anti-fibrotic effects of Resolvins. In an acute inflammatory response, resolvins (Rvs) inhibit the adhesion, migration, and infiltration of polymorphonuclear leukocytes (PMNs) and enhance the efferocytosis capacity of macrophages. D-series Rvs (RvD1 and RvD2) induce the polarization of macrophages toward to phenotype M2. One of the E-series Rvs, RvE1 blocks the migration and production of interleukin (IL)-12 in dendritic cells (DCs) and the infiltration of CD8+ and CD4+ cells. RvD1 and RvD2 suppress the inflammatory responses of CD8+ T, T helper (Th)1, and Th17 cells, in addition to limiting the differentiation of CD4+ T cells into T helper (Th)1 and Th17 cells and promoting the conversion of T regulatory (Treg) cells. 17-hydroxydosahexaenoic acid (17-HDHA) and RvD1 enhance the antibody secretion of B cells. After an inflammatory response, most of Rvs block the development of fibrosis by decreasing collagen deposition and myofibroblast infiltration, as well as by inhibiting epithelial-mesenchymal cell transition (EMT).