Resolution Mechanisms in Inflammatory Responses

Inflammation resolution is an active, highly coordinated programme that restores tissue homeostasis after injury or infection. It begins with the cessation of neutrophil recruitment and the clearance of apoptotic cells by macrophages, a process known as efferocytosis. Concurrently, there is a lipid-mediator class switch from pro-inflammatory eicosanoids to specialised pro-resolving mediators (SPMs) such as lipoxins, resolvins and maresins. Anti-inflammatory cytokines including IL-10 and IFN-β further reprogramme mononuclear phagocytes, while metabolic and epigenetic changes consolidate a pro-resolution phenotype. Translational control of key proteins and hypoxia-triggered signalling pathways—such as erythropoietin receptor activation—promote debris clearance and tissue repair. Dysregulation of these mechanisms underpins chronic diseases like rheumatoid arthritis, asthma and lymphedema, and has spurred the development of pro-resolution pharmacology and cell-based therapies to harness endogenous repair circuits and prevent pathological inflammation.

Research from Nature Portfolio

Recent studies have underscored the importance of lipid-modifying enzymes and cytokine networks in tissue-specific resolution. A 2024 investigation demonstrated that loss of 15-lipoxygenase activity in lymphatic endothelium leads to a deficit of specialised pro-resolving mediators and increased apoptosis of regulatory T cells in lymphedematous tissue. Administration of IFN-β restores both enzyme expression and Treg populations, revealing a therapeutic axis for lymphatic inflammation. A foundational review has compared universal and tissue-specific resolution programmes in chronic inflammatory diseases, highlighting distinct cellular pathways in joints, gut and lung and framing impaired resolution as a root cause of conditions such as Crohn’s disease and rheumatoid arthritis. Mechanistic insight has also emerged from studies showing that respiratory-burst-induced hypoxia activates macrophage erythropoietin signalling, which via PPARγ enhances efferocytosis, debris removal and migration to lymphoid tissues, thereby accelerating the resolution of acute inflammation.

Resolution Mechanisms in Inflammatory Responses publication trend

The graph below shows the total number of articles in resolution mechanisms in inflammatory responses across all publications each year (not limited to Nature Index journals).

Technical terms

Specialised pro-resolving mediators (SPMs): Endogenous lipid compounds derived from essential fatty acids that actively orchestrate the cessation of inflammation and stimulate tissue repair.

Efferocytosis: The phagocytic clearance of apoptotic cells by macrophages, crucial for preventing secondary necrosis and promoting resolution.

Resolution-phase macrophages: A distinct macrophage phenotype characterised by reduced pro-inflammatory activity and enhanced debris clearance and tissue-repair functions.

Regulatory T cells (Treg): A subset of T lymphocytes that modulate immune responses and contribute to inflammation resolution through anti-inflammatory cytokine production.

References

1. 15-Lipoxygenase promotes resolution of inflammation in lymphedema by controlling Treg cell function through IFN-β. Nature Communications (2024).
2. Resolution of chronic inflammatory disease: universal and tissue-specific concepts. Nature Communications (2018).
3. Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution. Nature Communications (2016).
4. Amelioration of experimental autoimmune encephalomyelitis by in vivo reprogramming of macrophages using pro-resolving factors. Journal of Neuroinflammation (2023).
5. Mmp12 Is Translationally Regulated in Macrophages during the Course of Inflammation. International Journal of Molecular Sciences (2023).