Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Our view of human mast cells has broadened. In the past, they were established as crucial effector cells of allergic inflammation; now, they are increasingly recognized as cells that regulate many tissue functions, such as blood flow and coagulation, smooth-muscle contraction and peristalsis of the intestine, mucosal secretion, wound healing and regulation of innate and adaptive immune responses, including tolerance. Laboratory tools to study human mast cells are limited; therefore, many mast-cell studies have been carried out using murine mast cells. This has not always been clearly indicated in review articles or in the titles of original articles. There are important functional differences between human and murine mast cells, such as receptor expression (for example, Fcγ receptors and functional TLRs), responsiveness to cytokines (for example, IL-3 and IL-4) and mediator expression (for example, proteases, IL-4, IL-5 and TNF). These differences limit extrapolation from murine data to the human situation. Human mast cells seem to be more closely related to monocytes and macrophages, whereas human basophils share properties mainly with eosinophils. Mast-cell inhibitors, such as ligands of ITIM-containing receptors (FcγRIIb and CD300a), the anti-inflammatory cytokines IL-10 and TGFβ1, CD200 and intracellular signalling molecules that modulate FcεRI-mediated mast-cell activation, are a new and exciting area of mast-cell research that is just starting to be unravelled for human mast cells. The role of mast cells in allergic inflammation is complex and is not restricted to the immediate phase of IgE-mediated reactions. Mast-cell mediators affect the mucosa, the blood vessels and sensory nerves at sites of allergy; mast-cell proteases and cytokines contribute to the initiation of a facultative late-phase reaction by recruiting and activating eosinophils, neutrophils and TH2 cells; and mast-cell-derived signals (such as IL-13 and CD40L) might contribute to IgE synthesis.