Specialized pro-resolving mediators and autoimmunity: Recent insights and future perspectives

Abstract

Inflammation is a response to injuries involving multiple cellular and molecular mechanisms. Different stimuli, such as trauma or microbial invasion, trigger an acute inflammatory response consisting, at least in principle, of two phases: initiation and resolution. Although the acute phase of inflammatory response represents a protective and usually self-limited mechanism, it can sometimes persist and evolve into chronic inflammation, a key driver in the development of many rheumatic and autoimmune diseases. The biosynthesis of specialized pro-resolving mediators (SPMs) orchestrates the resolution phase of inflammation, leading to the shutdown of phlogosis, tissue damage repair, and restoration of homeostasis. Dysregulation in SPMs biosynthesis or receptor expression and signalling are related to impaired viruses' clearance and adaptive immune response. Emerging knowledge on the involvement of SPMs in the development and progression of rheumatic diseases is arising. An altered SPM profile has been observed in different rheumatic diseases, including Rheumatoid Arthritis, Systemic Lupus Erythematosus, Adult-onset Still's Disease, Systemic Sclerosis, and Sjögren's Syndrome. Considering the anti-inflammatory and pro-resolving roles of these molecules, the possible use of synthetic SPMs and fish oil supplements, a crucial source of SPMs precursors DHA, DPA and EPA, in patients affected by chronic inflammatory diseases, is emerging.