Table 1.
Disease | Model | Immune Cell Type | Investigated Endpoints | Major Findings | Reference |
---|---|---|---|---|---|
UC | Human (10 patients) |
Colonic macrophages | ↑Gal-3 expression | Attenuation of acute colitis | [47] |
PBMCs | ↑Gal-3 secretion | ||||
Mice (DSS- induced acute colitis) |
↓ Macrophages in colon | Gal-3 blocking (Gal-3−/− ko mice or pharmacological inhibition): ↓NLRP3 inflammasome ↓inflammatory cytokines (IL-1β, TNF-α) ↑IL-10 producing M2 phenotype |
|||
↓DCs in colon | |||||
↓ Neutrophils in colon | |||||
UC | Mice (DSS- induced acute colitis) |
Colonic macrophages | Gal-3 blocking in MSC (pharmacological inhibition): ↑ immunosuppressive M2 phenotype ↑IL-10 |
Attenuation of severity of colitis | [91] |
UC | Mice (DSS- induced colitis) |
T cells | Gal-3 blocking (Gal-3−/− ko mice): ↑ severe disease activity Recombinant Gal-3: ↑ Treg cell phenotype (FOXP3, ICOS, and PD-1 positive) Adoptive transfer of Gal-3 treated T cell: ↓Inhibition of colonic mucosa inflammation |
Reduction of disease severity by inducing Treg | [92] |
UC | Mice (DSS- induced colitis) |
Mesenteric lymphnodes |
|
[93] | |
UC | Mice (DSS- induced colitis) |
Macrophages | Gal-3 blocking (Gal-3−/− ko mice): ↓ IL-1-, TNF-α, IL-6 and IL-12-producing M1 phenotype ↑ IL-10-, IL-4, and TGF-β- producing M2 phenotype |
Reduction of colon inflammation | [46] |
DCs | Gal-3 blocking in DCs (pharmacological inhibition): ↑ DCs immunosuppressive function |
||||
T cells | ↑ colon-infiltrated Tregs ↑pro-inflammatory Th1/Th17 phenotype |
||||
CRC | In vitro, colon cancer cell lines from CRC patients | T cells | Recombinant Gal-3: ↓ tumor-reactive T cells ↑ cell apoptosis |
Promotion of tumor immune tolerance | [94] |
CRC | Mice (Gal-3−/− ko) |
↓ Macrophages in colon | ↑IL-6, KC |
|
[95] |
↓ DCs in colon | |||||
↓ T cells in colon | |||||
= Neutrophils in colon | |||||
CRC | Human (50 patients) |
PBMCs | ↑Gal-3 secretion ↑ IL-17 and IL-10 ↓ IL-12 ↑inflammatory parameters (NLR, WBC, CRP) ↓limphocytestimulation |
|
[96] |
CRC | In vitro, colon cancer cell lines (HT29, LS180, SW948, SW620) |
Monocytes (THP1 cells) |
↑Gal-3 and IDO induction by tumor CM | Induction of immune suppressive macrophages | [97] |
Abbreviations: CM, conditioned medium; CRC, colorectal cancer; CRP, C-reactive protein; DCs, dendritic cells; DSS, dextran sulphate sodium; IBD, inflammatory bowel disease; IDO, indoleamine 2,3-dioxygenase; KC, keratinocyte-derived chemokine; ko, knock out; NLR, neutrophil/lymphocyte ratio; PBMC, peripheral blood mononuclear cells; siRNA, short interfering RNA; Treg, regulatory T cells; UC, ulcerative colitis; WBC, white blood cell count.