Table 1.
Selected cytokine activities implicated in the pathogenesis of IBD and fungal immunity
| Cytokine | Source in the mucosa | Potential function in the pathogenesis of intestinal inflammation | Potential function against mucosal fungi |
|---|---|---|---|
| IL-1 | Phagocytes, ILCs, and IECs | Promote Th1 and Th17 differentiation, and IFN-γ secretion; increase the survival of IECs | Promote Th1 and Th17 differentiation, and IFN-γ secretion; modulate Group 3 ILCs to produce IL-22 |
| IL-4 | T cells | Intestinal fibrosis; tissue remodeling | Induce IL-12-dependent Th1 responses; suppress protective immune responses to Aspergillus fumigatus and Histoplasma capsulatum |
| IL-6 | Phagocytes, ILCs, and IECs | Increase the survival of IECs, Th1, Th2, or Th17 CD4+ T cells; increase the survival of IECs and anti-microbial peptide secretion | Neutrophil recruitment; augmenting Th1-mediated immunity |
| IL-10 | Dendritic cells and T cells | Balancing polymorphonuclear leukocyte-regulatory T-cell interaction; tissue fibrosis | Inhibit the fungicidal activity of monocytes and neutrophils; induce IL-12-dependent Th1 cells and Treg cells |
| IL-13 | T cells | Intestinal fibrosis; impair epithelial barrier | Oxidative burst; phagocytosis; induce tolerance to Cryptococcus neoformans |
| IL-17 | T cells (Th17) | Intestinal fibrosis; recruit neutrophils; anti-microbial peptide secretion; intestinal barrier survival | Neutrophil recruitment; natural killer cells trafficking; upregulate Treg and Th1 responses |
| IL-18 | Phagocytes, ILCs, and IECs | Disrupt goblet cells maturation and function; increase the survival of IECs; induce anti-tumorogenic T-cell responses | Induce anti-tumorogenic T-cell responses |
| IL-22 | T cells (Th17, ILCs, Th1, and natural killer T cells) | Intestinal barrier repair; tissue fibrosis; mucosal injury; anti-microbial peptide secretion | Upregulate Treg and Th1 responses; induce inflammation in response to intestinal Candida albicans |
| IL-23 | Phagocytes, ILCs, and IECs | Expansion and survival of Th17, natural killer cells, and ILCs | Promote Th1 and Th17 differentiation; upstream of IL-17 and IL-22 |
| IL-33 | IECs and sub-epithelial myofibroblasts | Induce inflammation during early stages of acute colitis; generate a shift towards Th2 immune reactions; increase the survival of IECs | Increase neutrophil phagocytic activity; shift immune responses toward M2 macrophages; induce Treg differentiation |
| IL-35 | Dendritic cells | Upregulate Treg cells and Th17 | Upregulate Treg cells; suppress inflammation; p35-dependent antifungal response downstream of IL-22 |
| TNF-α | Innate immune components; T cells | Weaken barrier function; suppress T-cell apoptosis; neutrophil recruitment | Neutrophil recruitment; increase T-cell survival |
| IFN-γ | Innate immune components; T cells | Suppress T-cell apoptosis; neutrophil recruitment | Neutrophil recruitment |
IBD = inflammatory bowel disease, IECs = intestinal epithelial cells, IFN-γ = interferon-gamma, IL = interleukin, ILCs = innate immune cells, Th = T helper, TNF-α = tumor necrosis factor-alpha, Treg = T regulatory.