Leukotriene B4 Signaling in Immune Regulation

Leukotriene B4 (LTB4) is a potent lipid mediator derived from arachidonic acid that orchestrates key events in innate and adaptive immunity. Synthesised by 5-lipoxygenase in activated myeloid cells, LTB4 binds two principal G protein-coupled receptors: BLT1, a high-affinity receptor on neutrophils, monocytes and select lymphocyte subsets; and BLT2, a low-affinity receptor with wider tissue distribution. Engagement of these receptors triggers calcium mobilisation, chemokine and cytokine release, integrin activation and directed cell migration. Through these mechanisms, LTB4–BLT1/BLT2 signalling amplifies neutrophil swarming, supports macrophage recruitment and modulates dendritic cell function, thereby influencing antigen presentation and T-cell polarisation. Balanced LTB4 activity is essential for effective microbial clearance and for the timely resolution of inflammation; dysregulation contributes to chronic inflammatory diseases, autoimmune pathology, glomerulonephritis, tumour-promoting microenvironments and acute lung injury. Genetic ablation or pharmacological inhibition of LTB4 receptors has revealed therapeutic potential in preclinical models, underscoring the axis as a central node in immune regulation.

Research from Nature Portfolio

Recent studies have illuminated the role of LTB4 signalling in the tumour microenvironment, including the discovery that activation of the LTB4 receptor 2 on hepatic stellate cells drives a β-catenin–YAP1 cascade essential for liver tumourigenesis. Inhibition of this receptor attenuates tumour growth by disrupting paracrine release of eicosanoid ligands and downstream oncogenic pathways. Additional work has elucidated how LTB4 receptor functions constrain acute lung injury: loss of receptor-mediated signalling leads to enhanced vascular leakage and bronchoconstriction through unrestrained cysteinyl leukotriene activity, revealing protective cross-talk between lipid mediator pathways.

Leukotriene B4 Signaling in Immune Regulation publication trend

The graph below shows the total number of articles in leukotriene b4 signaling in immune regulation across all publications each year (not limited to Nature Index journals).

Technical terms

Leukotriene B4 (LTB4): a bioactive lipid mediator derived from arachidonic acid that functions as a potent chemoattractant for leukocytes.

BLT1: a high-affinity G protein-coupled receptor for LTB4 predominantly expressed on neutrophils, monocytes and other immune cells.

BLT2: a low-affinity receptor for LTB4 and related eicosanoids with broader tissue expression and distinct signalling properties.

Chemoattractant: a soluble factor that directs cell migration by forming concentration gradients.

Chemotaxis: the process by which cells move directionally in response to a chemical gradient.

Eicosanoids: a class of oxygenated polyunsaturated fatty acid derivatives, including leukotrienes, prostaglandins and thromboxanes, that regulate inflammation and immunity.

References

1. Hepatic stellate cell stearoyl co-A desaturase activates leukotriene B4 receptor 2 - β-catenin cascade to promote liver tumorigenesis. Nature Communications (2023).
2. Two distinct forms of human BLT2: long-form and short-form BLT2. Frontiers in Cell and Developmental Biology (2023).
3. Leukotriene B4 receptor 2 governs macrophage migration during tissue inflammation. Journal of Biological Chemistry (2023).
4. The leukotriene B4/BLT1‐dependent neutrophil accumulation exacerbates immune complex‐mediated glomerulonephritis. The FASEB Journal (2023).
5. Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury. Scientific Reports (2016).