Table 2.

Ligands for the FFA4 receptor, signaling pathways, and effects on immune cells.

Action	Ligand	Effects on immune cells	References
Natural agonist	DHA, EPA	↓ proliferation, migration, IL-2, IFN-γ, IL-17, IL-10, NF-κB, PKC; ↑ calcium, PPAR, apoptosis, ROS in T-cells.	Verlengia et al., 2004; Denys et al., 2005; Yessoufou et al., 2009; Unoda et al., 2013; Zhelev et al., 2016; Cucchi et al., 2020; Saidi et al., 2020
		↑ phagocytosis, TNF-α, IL-1β, MMP-9, ROS, calcium; ↓ IL-8, ROS, calcium and NF-κB in neutrophils.	Fickl et al., 2005; Gorjao et al., 2006; Pisani et al., 2009; Paschoal et al., 2013; Olmo et al., 2019
		↓ HDACs, Inflammasome, IL-1, TAK1, MKK4, NF-κB, p38 MAPK, ERK, JNK;↑ M2 macrophages.	Rahman et al., 2008; Oh et al., 2010; Xue et al., 2012; Li et al., 2013; Pham et al., 2018; Kasonga et al., 2019; Kawano et al., 2019; Wierenga et al., 2019
Synthetic agonist	TUG-891	↑ calcium, MMP-9 and ROS in neutrophils.	Olmo et al., 2019
		↑ M2 markers; ↓ M1 markers, motility and phagocytosis in macrophages.	Hudson et al., 2013; Wang et al., 2019a; Zhao et al., 2019; Su et al., 2020
	Grifolic acid	↓ viability, ATP and MMP in macrophages.	Zhao et al., 2018
	GSK 137647	↓ MMP-9, MMP-3, TIMP-1 and migration in macrophages.	Hasan et al., 2017
	Compound A	↓ NF-κB, TNF-α, IL-6 and chemotaxis, in macrophages.	Oh et al., 2014
	KDT501	↓ IL-6, IL-10, MCP-1 and RANTES in macrophages.	Konda et al., 2014
Antagonist	AH7614	↓ Calcium and ROS in neutrophils.	Olmo et al., 2019

↑, increases; ↓, decreases.