Table 1: Regulators of innate immune cell responses during type 2 inflammation.
Factors discussed in the text (list not exhaustive) that regulate basophil, mast cell, ILC2, DC, or eosinophil functions during type 2 inflammation. Cellular targets and supporting references cited in the text are highlighted, with possible cellular sources indicated.
| Factor | Function during type 2 inflammation | Known or proposed direct cellular targets and supporting references | Cellular sources (secreted factors only) |
|---|---|---|---|
| Adenosine | Promotes IL-33 production | Unclear in vivo [140] | Damaged tissue stromal cells? |
| β7 integrin | Promotes cell accumulation in the small intestine | Mast cells [122] | NA |
| CCR3 ligands (ie. eotaxin) | Elicits cell migration | Mast cells, eosinophils [47,48] | DCs, macrophages |
| GM-CSF | Supports cell survival (effect in vivo remains unclear) | Eosinophils [61] | Activated T cells, mast cells, macrophages, ILC2s |
| IgG | Promotes anti-parasite effector responses | Mast cells [129] | B cells |
| IgE | Elicits degranulation and promotes type 2 cytokine production | Basophils, mast cells [58,124-126 (reviews)] | B cells |
| IL-2 | Supports cell proliferation and survival | ILC2s [63,69,70] | T cells, ILCs |
| IL-3 | Promotes cell differentiation, survival, and activation | Basophils, mast cells [55-57; 50,52,58 (reviews)] | T cells |
| IL-5 | Promotes cell accumulation in tissues, survival, and type 2 cytokine production |
Eosinophils [61; 59,60 (reviews)] | Th2 cells, eosinophils, mast cells |
| IL-7 | Supports cell differentiation and survival | ILC2s [62,63,65,66,68; 51,67 (reviews)] | Stromal cells |
| IL-18 | Suppresses cell survival and type 2 cytokine production | Mast cells [41; 42 (review)] | Macrophages, DCs, epithelial cells (active or precursor forms) |
| IL-25 | Promotes cell accumulation in tissues, activation, and type 2 cytokine production and potentiates degranulation | Basophils, ILC2s, eosinophils [18-21,27,36,79,107,109,117,149; 8 (review)] | Tuft cells, granulocytes |
| IL-33 | Promotes cell accumulation in tissues, activation, survival, and type 2 cytokine and prostaglandin production or release | Basophils, mast cells, ILC2s, DCs, eosinophils [22,23,25,35-38,54,78,79,88,107,144,146,148,153-155; 8,13,141 (reviews)] | Epithelial and myeloid cells |
| Leukotrienes (LTs) | Promote cell accumulation in tissues and type 2 cytokine production | ILC2s, eosinophils [80,82,84,88,146; 86,87 (reviews)] | Mast cells, basophils, eosinophils |
| MHC II interactions | Support cell proliferation, enable interactions with T cells, and promote type 2 cytokine production | Basophils (?), ILC2s, DCs [63,103-105,109; 98,99 (reviews)] | NA |
| NMU | Promotes cell accumulation in tissues, activation, and type 2 cytokine production | Mast cells, ILC2s, eosinophils [130-132,135,136] | Neurons |
| Notch signaling | Controls cell differentiation and tissue localization and promotes type 2 cytokine production | Basophils, mast cells, ILC2s [114-119] | NA |
| PGD2 | Promotes cell accumulation in tissues, activation, chemotaxis, and type 2 cytokine production | Basophils, mast cells, ILC2s, eosinophils [74,79,81,85,90,91,93; 67,75,92 (reviews)] | Mast cells |
| PGE2 | Supports Th2 polarizing capacity and promotes IL-33 production | DCs [89,145,153,154] | Mast cells |
| Sphingosine 1 phosphate | Promotes chemotaxis | ILC2s [95] | Platelets, erythrocytes, endothelium, hepatocytes |
| TL1A | Promotes cell accumulation in tissues, activation, survival, and type 2 cytokine production | ILC2s [39,40] | T cells, myeloid, epithelial, and endothelial cells |
| TSLP | Supports Th2 polarizing capacity and promotes type 2 cytokine, chemokine, and prostaglandin production or release | Basophils, mast cells, ILC2s, DCs [26,31,143,144,150-152; 12 (review)] | Epithelial and myeloid cells |