Table 1.
Mast-cell immunomodulatory functions demonstrated in vivo*
| Immunomodulatory functions | Mast cell mediators involved (if identified) | Comments | References† |
|---|---|---|---|
| Positive: | |||
| Promote recruitment of cells of innate immunity | TNF, CXCL2, leukotrienes, mMCP1, mMCP2, mMCP6. | In some studies (REFS60,63,67,68,70) the TNF was shown to be of mast cell origin by analyzing mice containing mast cells that could or could not make TNF; in the other studies, the TNF was not formally shown to be of mast cell origin. | 28,32,33,57-61,64,69,76 |
| Promote lymphocyte recruitment | TNF | 62,64,67,68,70,72,92 | |
| Promote DC migration | Histamine, TNF | 62,64,65,71,92 | |
| Promote pathology in EAE via enhancement of TH1-cell response | IL-4 | 54 | |
| Enhance sensitization in CHS¶ | Mediator unknown | Some in vivo studies strongly suggest that mast cells promote sensitization due to an effect, induced by the binding of antigen-non-specific IgE antibodies to mast-cell FcεRI, on mast-cell phenotype and/or function. | 88 |
| Promote a model of antibody-mediated arthritis | IL-1 | 66 | |
| Negative: | |||
| Suppress adaptive immune responses | Histamine, IL-10 | 23,49,82,93 | |
| Promote peripheral tolerance to skin allografts | IL-10? | 83 | |
| Suppress innate responses (to chronic UVB irradiation) | IL-10 | 23 |
Representative functions demonstrated in experiments performed in vivo using either mouse mast-cell protease-deficient mice or mast-cell-engrafted c-kit mutant mice (mast-cell knock-in mice). In some models using mast-cell knock-in mice, the key mast-cell mediators with immunomodulatory functions in that model have not yet been defined. Not included herein are many examples of studies using ‘mast-cell knock-in mice’ that have demonstrated pro-inflammatory effects of mast cells (for example promotion of leukocyte recruitment), but in which the key mast-cell-associated mediators have not yet been defined in vivo.
In some of the referenced studies, the mast-cell mediators that contribute to the function listed have not yet been identified.
Not yet demonstrated using mast-cell-knock-in mice.
CHS, contact hypersensitivity; CXCL2, CXC-chemokine ligand 2; DC, dendritic cell; EAE, experimental autoimmune encephalomyelitis; FcεRI, high-affinity Fc receptor for IgE; IL, interleukin; mMCP1, mouse mast-cell protease-1; TH1, T helper 1; TNF, tumour-necrosis factor.