New models for analyzing mast cell functions in vivo

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Trends in Immunology (Impact Factor: 12.03). 11/2012; 33(12). DOI: 10.1016/
Source: PubMed

ABSTRACT In addition to their well-accepted role as critical effector cells in anaphylaxis and other acute IgE-mediated allergic reactions, mast cells (MCs) have been implicated in a wide variety of processes that contribute to disease or help to maintain health. Although some of these roles were first suggested by analyses of MC products or functions in vitro, it is critical to determine whether, and under which circumstances, such potential roles actually can be performed by MCs in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products during biological responses in vivo, and comments on some of the similarities and differences in the results obtained with these newer versus older models of MC deficiency.

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    ABSTRACT: Mast cells (MCs) are cells of hematopoietic origin that normally reside in mucosal tissues, often near epithelial cells, glands, smooth muscle cells, and nerves. Best known for their contributions to pathology during IgE-associated disorders such as food allergy, asthma, and anaphylaxis, MCs are also thought to mediate IgE-associated effector functions during certain parasite infections. However, various MC populations also can be activated to express functional programs-such as secreting preformed and/or newly synthesized biologically active products-in response to encounters with products derived from diverse pathogens, other host cells (including leukocytes and structural cells), damaged tissue, or the activation of the complement or coagulation systems, as well as by signals derived from the external environment (including animal toxins, plant products, and physical agents). In this review, we will discuss evidence suggesting that MCs can perform diverse effector and immunoregulatory roles that contribute to homeostasis or pathology in mucosal tissues.Mucosal Immunology advance online publication, 11 February 2015; doi:10.1038/mi.2014.131.
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    Dario A Gutierrez, Sathya Muralidhar, Stephan Herzig, Hans-Reimer Rodewald
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    ABSTRACT: Graphical Abstract Highlights d Obesity and insulin resistance are unaffected by mast cell deficiency d Global Kit deficiency protects mice from obesity and associated metabolic disorders d Reconstitution of Kit mutant mice with Kit +/+ HSCs normalizes metabolic phenotype In Brief Mice with Kit mutations have several immune and non-immune abnormalities, including mast cell deficiency, and are protected from weight gain and insulin resistance during diet-induced obesity. Gutierrez et al. show that this protection is not mediated by mast cell deficiency, as previously thought, but instead through hematopoietic Kit deficiency.