Mast Cell Homeostasis: A Fundamental Aspect of Allergic Disease

Abstract

Mast cells are well known for their role in allergic disease and have recently been implicated in inflammatory disorders, including autoimmune arthritis, multiple sclerosis, and atherosclerosis. Although aberrant mast cell activation is the focus of many studies, much less is known about normal mast cell homeostasis. Because loss of the normal constraints on mast cell activation, proliferation, and survival may be central to disease etiology, understanding these issues warrants attention. This review summarizes the knowledge of mast cell homeostasis controlled by IgE and the regulatory cytokines IL-4, IL-10, and TGF-beta1. Because each of these proteins plays an important role in immune responses tied to mast cell-associated disease, this group represents a potential set of factors altered in atopic or autoimmune patients. It is interesting to note, for example, that polymorphisms within each of these factors or their receptors are linked to allergic disease. By first understanding how cytokines and IgE regulate mast cell function and survival, we may then predict how these factors may function in disease onset and progression.

Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-α

“…Mast cell activation by specific antigen induces the cells to release spasmogenic, vasoactive and proinflammatory mediators, which in turn can enhance airway smooth muscle contraction, vascular permeability, and inflammatory cell (T cells, dendritic cell, neutrophils, eosinophils, and monocytes) recruitment at sites of antigen challenge (Biedermann et al, 2000;Bradding et al, 2006;Suto et al, 2006;Kneilling et al, 2009). Chemokines and cytokines are also released and induce neutrophil influx upon injection of cytokines, such as TNF-α (Ryan et al, 2007;Kawakami et al, 2009). On the other hand, locally released chemokines may activate resident cells to release cytokines.…”

Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

“…Increased recruitment and/or retention, as well as local maturation of mast-cell progenitors, can also contribute to the expansion of mast-cell populations in the tissue [15][16][17][18] (Figure 1). In addition, expansion of mastcell numbers, as well as local changes in their tissue distribution and/or phenotypic characteristics, can occur during T helper 2 (T H 2)-cell responses, persistent inflammation and/ or tissue remodelling [15][16][17][18] (Figure 1). Such T H 2-cell responses are often associated with an increase in the number of circulating basophils, which are haematopoietic cells developmentally distinct from mast cells but that can secrete various mediators, including histamine, that are also produced by mast cells.…”

“…Furthermore, mast cells can participate in multiple cycles of activation for mediator release and can be differentially activated to release distinct patterns of mediators or cytokines, depending on the type and strength of the activating stimuli 1,6,13,18,20,21 . The strength and nature of the responsiveness of mast cells to various activating stimuli may be influenced by genetic or microenvironmental factors that affect the expression pattern or functional properties of the surface receptors or signalling molecules that contribute to such responses 1,4,20 .…”

“…Mast cells represent potential sources of many mediators that can enhance or suppress the development, survival, proliferation, migration, maturation, or function of immune cells (reviewed in REFS [1][2][3][5][6][7][8]13,[16][17][18]21,30,31,43,44,[46][47][48][49][50][51][52][53][54][55][56]. Some individual mediators, such as histamine, can have both positive and negative immunomodulatory effects.…”

Rab5a Regulates Surface Expression of Fc.EPSILON.RI and Functional Activation in Mast Cells

“…3,4) The constitutive cycling of transmembrane proteins such as receptors, channels and transporters has recently been demonstrated in a wide range of cell types, 5) which is thought to be important as a determinant of surface expression levels of these proteins.…”