Regulation of T-Cell Immune Responses by Pro-Resolving Lipid Mediators

Abstract

Both the initiation and the resolution of inflammatory responses are governed by the sequential activation, migration, and control/suppression of immune cells at the site of injury. Bioactive lipids play a major role in the fine-tuning of this dynamic process in a timely manner. During inflammation and its resolution, polymorphonuclear cells (PMNs) and macrophages switch from producing pro-inflammatory prostaglandins and leukotrienes to specialized pro-resolving lipid mediators (SPMs), namely, lipoxins, resolvins, protectins, and maresins, which are operative at the local level to limit further inflammation and tissue injury and restore homeostasis. Accumulating evidences expand now the role and actions of these lipid mediators from innate to adaptive immunity. In particular, SPMs have been shown to contribute to the control of chronic inflammation, and alterations in their production and/or function have been associated with the persistence of several pathological conditions, including autoimmunity, in human and experimental models. In this review, we focus on the impact of pro-resolving lipids on T cells through their ability to modulate T-cell responses. In particular, the effects of the different families of SPMs to restrain effector T-cell functions while promoting regulatory T cells will be reviewed, along with the underlying mechanisms. Furthermore, the emerging concept of SPMs as new biological markers for disease diagnostic and progression and as putative therapeutic tools to regulate the development and magnitude of inflammatory and autoimmune diseases is discussed.

Specialized Pro-Resolving Mediators Reduce Scarring After Cleft Lip Repair

“…In addition, T-cells derived from keloid scar tissue were abnormal compared with normal skin tissue ( 69 ). The positive therapeutic impact of LXA 4 -ME on scarring after cleft lip repair could be via modulating T-cell responses and decreasing their proinflammatory activities as it has been shown in other T-cell-mediated immune diseases ( 24 ). The mechanisms of SPMs on regulating the proliferation of fibroblasts, myofibrobasts and muscular cells to promote scarless wound healing are yet to be discovered.…”

“…SPMs can foster wound healing and tissue regeneration through their anti-inflammatory and pro-resolving actions by limiting neutrophil influx and activity, improving phagocytosis by macrophages and decreasing pro-inflammatory cytokine production, stimulating the clearance of inflammatory debris and promoting the return to tissue homeostasis ( 22 , 23 ). SPMs can also modulate T-cell responses by decreasing their proinflammatory activities and promoting Treg cells, supporting SPM-based therapy as a promising avenue for the treatment of a wide range of T-cell-mediated immune and autoimmune diseases ( 24 ). SPMs can also mediate the crosstalk between glial cells and neurons suggesting new therapeutic strategies for different diseases of the CNS that need to be explored further ( 25 ).…”

Specialized Pro-Resolving Lipid Mediators: New Therapeutic Approaches for Vascular Remodeling

“…GPR37 is expressed in macrophages and its activation by NPD1 enhances macrophage phagocytic activity and resolution of inflammatory pain [ 48 ]. Moreover, exogenous SPMs have been found to reduce T-cell recruitment and infiltration into target organs and decrease activation and inflammatory cytokine production [ 68 , 69 ]. Interestingly, human platelets also express the SPM receptors GPR32, ALX–FPR2 and ChemR23, which modulate aggregation, clot remodeling and platelet–PMN interactions.…”

Lipids in Liver Failure Syndromes: A Focus on Eicosanoids, Specialized Pro-Resolving Lipid Mediators and Lysophospholipids

“…These cells are indeed involved in class switching of lipid mediators after eicosanoids storm as firstly described more than 20 years ago ( 7 ). SPMs also prevent chronic inflammation and autoimmunity by limiting the persistent activation and the autoreactive responses of almost all subsets of T lymphocytes ( 134 – 136 ). As eicosanoids, SPMs are synthesised from PUFA detached from the membrane by the action of PLA2.…”