Table 2.

Major effects of n-3 PUFA- and SFA-enriched diets on innate and adaptive immune cells in animal models and clinical trials.

Diet	Cell Type	In Vivo Effect	Ref.
n-3 PUFA-rich diet	Epithelium	↑ Barrier function in the mouse model of intestinal anaphylactic response	[37]
		↓ Inflammatory score, ↑ TJ proteins expression (ZO-1 and Occludin), ↓ IL-17, TNF-α and IFN-γ production in the IL-10-deficient model of chronic colitis	[38]
		↓ Intestinal pathology scores and IL-12, TNF-α, IL-1β secretion and ↑ of ZO-1 expression in SCID mice in the model of colitis	[39]
		↓ Oxidative stress (8-IP, glutathione and iNOS) in a rat model of colitis	[40]
		↑ Healing capacity during dust-stimulated lung inflammation	[42]
	Macrophages	↓ Frequency of ATMs and ↑ M2 anti-inflammatory phenotype and ↑ expression of IL-10, arginase, YM-1, Clec7a and MMR	[72]
		↑ Phagocytosis, microbicidal activity and ↓ apoptosis	[106,107]
		↓ NLRP3 inflammasome activation via GPR120 and GPR40 receptors and their downstream protein β-arrestin-2	[108,109]
		↑ Autophagy	[110]
	Dendritic cells	↓ Capacity to stimulate proliferation of antigen-specific T cells and their Th1/Th17 differentiation	[75]
		↓ Antigen-presenting properties and ↓ CD2+ DCs, and ↓ CD18, CD11a, HLA-DR, CD54 expression	[111]
		↓ CD80 and CD11c+ expression, ↓ TNF-α production and ↓ phagocytosis	[112]
		↓ Th1-inducing, pro-inflammatory (CD11c+ CD11b− CD8α+) lymphoid DCs and ↑ myeloid, tolerogenic (CD11c+ CD11b+ CD8α−) DCs subpopulations	[112,113]
		↓ T cell proliferation and ↓ IFN-γ and IL-17 production in the DC-lymphocyte reaction	[114]
	Neutrophils	Protection during S. aureus sepsis, with ↓ mortality and bacteria load	[115]
		↑ CD11bhigh, Ly6Ghigh and MHC class IIhigh neutrophil subpopulation in the blood	[116]
		↑ Specialized pro-resolving mediators, such as 18-HEPE, RvE1, RvE2, RvE3, 17-HDHA and RvE5	[117]
		↑ Neutrophil telomere length, probably due to ↓ oxidative stress	[118]
		↑ Membrane integrity, ↓ ROS production, and mitochondrial membrane potential after exercise	[119]
		↑ Functions and frequency in oncologic patients undergoing chemotherapy	[120]
		↑ Neutrophil-dependent inflammation in mice genetically susceptible to colitis	[121]
	T cells	↓ Proliferation via ↓ IL-2 secretion and IL-2RA expression	[122]
		↓ Production of diacylglycerol, ceramide, and level of phospholipase Cγ	[122]
		Disrupted spatial organization of the second messenger, PI(4,5)P2, perturbing downstream signals required for T cell proliferation	[123]
		↓ Frequency of pro-inflammatory T cells in the fat tissues, mediated by CCR-4, CXCR4 and ↓ expression of P-selectin and ICAM-1 on the endothelium	[66,124]
		↓ Formation of pseudopods and ↓ ratio between F-actin and G-actin and ↓ Rhoα and Rac1 involved in cell migration	[125]
		↓ IL-6, IL-23, IL-17 expression and ↑ FoxP3, CTLA-4, TGF-β and IL-10 expression	[66,126,127]
		↓ Treg-dependent proliferation of T effector cells mediated by ↓ of ERK1/2 and Akt phosphorylation and ↑ histone deacetylase and p27Kip1 expression	[66]
	B cells	↑ CD69 and CD40 expression	[103,128]
		↑ IL-6, IFN-γ, TNF-α and IL-10, IL-5, IL-13, and IL-9 expression	[103,128,129]
		↑ Percentage of splenic transitional, marginal zone B cells and peritoneal B1 cells	[130,131]
		↑ Surface expression of IgM in spleen and serum	[130,131]
		↑ Caecal IgA	[128]
		Changed lipid composition of B cells and ↑ size, order and the distribution of rafts	[128,129,132]
SFA-rich diet	Dendritic cells	↓ Tolerogenic (CD11c+ CD103+ CD11b+) and ↑ pro-inflammatory (CD11c+ CD103− CD11b+) subpopulations in the gut	[133]
		↑ TLR4-dependent NLRP3 inflammasome activation and IL-1β secretion	[134]
	Neutrophils	↓ Survival rate and ↑ bacterial proliferation in septic mice	[135]
		↓ Cell frequency, ↓ phagocytosis and ↓ ROS production in septic mice	[135]
	T cells	↑ CXCR3 and ↓ CCR7 and L-selectin expression	[99]
		↑ Severity of the disease, ↑ Th1, and Th17 cell differentiation and ↑ T cell infiltration into the central nervous system	[101,136]
		Positive association with several markers of inflammation, such as C-reactive protein, IL-1RA, IFN-γ and CCL5	[137]

Table summaries studies with the observed (positive/negative) effects of n-3 PUFA- and SFA-enriched diets on innate and adaptive immune cells in animal models and clinical trials. For studies showing null results, see the text. ↓—downregulation or decrease; ↑—upregulation or increase; 17-HDHA—17-Hydroxydocosahexaenoic Acid; 18-HEPE—18-Hydroxyeicosatetraenoic Acid; 8-IP—8-Isoprostane; Akt—Protein Kinase B; ATMs—Adipose Tissue Macrophages; CCL5—C-C Chemokine Ligand 5; CCR-4—C-C Chemokine Receptor Type 4; CCR7—C-C Chemokine Receptor 7; CD—Cluster of Differentiation; CD11b—Integrin Alpha M; Clec7a—C-type Lectin Domain Family 7 Member A; CTLA-4—Cytotoxic T-Lymphocyte-Associated Protein 4; CXCR3—C-X-C Chemokine Receptor Type 3; CXCR4—C-X-C Chemokine Receptor Type 4; DCs—Dendritic Cells; ERK—Extracellular Signal-Regulated Kinases; FoxP3—Forkhead Box Protein 3; GPR120—G-Protein Coupled Receptor 120; GPR40—G-Protein Coupled Receptor 40; HLA-DR—Human Leukocyte Antigen—DR Isotype; ICAM-1—Intercellular Adhesion Molecule 1; IFN-ɣ—Interferon-Gamma; IgA—Immunoglobulin A; IgM—Immunoglobulin M; IL—Interleukin; IL-1RA—Interleukin 1 Receptor Antagonist; IL-2RA—Interleukin 2 Receptor Alpha Chain; iNOS—Nitric Oxide Synthase; Ly6G—Lymphocyte Antigen 6 Complex Locus G6D; MHC class II—Major Histocompatibility Complex Molecules Class II; MMR—Macrophage Mannose Receptor; NLRP3—NOD-like Receptor Protein 3; p27^Kip1—Cyclin-Dependent Kinase Inhibitor 1B; PI(4,5)P2—Phosphatidylinositol-4,5-Bisphosphate; PUFAs—Polyunsaturated Fatty Acids; ROS—Reactive Oxygen Species; RvE—Resolvin E; SCID—Severe Combined Immunodeficiency; SFAs—Saturated Fatty Acids; TGF-β—Tumor Growth Factor Beta; Th1—Type 1 T helper Cells; Th17—Type 17 T helper Cells; TJs—Tight Junctions; TLR—Toll-like Receptor; TNF-α—Tumor Necrosis Factor-Alpha; Treg—T Regulatory Cells; ZO-1—Zonula Occludens 1. Clinical trials are presented in italics.