MCCIR AZ GSK Update Seminar Series
|Dates:||14 December 2015|
|Times:||15:30 - 16:30|
|What is it:||Seminar|
|Organiser:||Faculty of Life Sciences|
|Who is it for:||University staff, Adults, Current University students|
|Speaker:||Rajia Bahiri, Michelle Campbell|
Mast cell-mediated regulation of T cell activities
Mast cells (MCs) are recognized to participate in the regulation of innate and adaptive immune responses. Owing to their strategic location at the host–environment interface, they control tissue homeostasis and are key cells for starting early host defense against intruders. Upon degranulation induced, e.g., by immunoglobulin E (IgE) and allergen-mediated engagement of the high-affinity IgE receptor, complement or certain neuropeptide receptors, MCs release a wide variety of preformed and newly synthesized products. Mast cell activation is associated with atopic diseases. Interestingly, increasing evidence suggests a regulatory role for MCs in inflammatory diseases via the regulation of T cell activities. Our work focus on the regulatory effect of Mast cells on T cells. We have demonstrated that MCs induced antigen-specific CD8+ T cell activation and proliferation. This process required direct cell contact and MHC class I-dependent antigen cross-presentation by MCs and induced the secretion of cytokine and increased their cytotoxicity. Furthermore, MC can also induce antigen specific activation and proliferation of CD4+ T cells. In addition, upon cytokine treatment mast cells expressed molecules that could be involved in stimulation or co-stimulation of immune cell. Thus, rather than only serving as effector cells, MCs are important players in regulation of T cells.
Understanding the roles of Mast Cell proteases in skin inflammation
Mast cells have principally been viewed in the context of allergy; however, recent findings implicate mast cells in both the homeostasis and pathophysiology of the skin, including psoriasis a disease in which mast cells are implicated. As cells with the capacity to both degranulate quickly to release pre-formed mediators and to de novo synthesise both pro and inflammatory mediators the way in which mast cells contribute to modulating their surroundings is an area of ongoing research. One of the main constituents produced by mast cells are proteases of the tryptase, chymase and elastase substypes. These proteases are released upon degranulation as soluble mediators, with the exception of transmembrane tryptase gamma (TMT?, TPSG1, Prss31), which is expressed on the cell surface and potentially shed. Soluble mast cell proteases are already known to be important in pathological conditions at other sites, with mouse mast cell protease-1 (mMCP-1), a chymase, being critical to worm expulsion in the Trichinella spiralis mouse model (1) and mMCP-6 and -7, tryptases, being implicated in the mBSA/IL-1? model of arthritis (2). Furthermore, the membrane bound tryptase, TMT?, has recently been shown to be detrimental in both the dextran sodium-sulfate (DSS) model of colitis and the cigarette smoke induced model of chronic obstructive pulmonary disease (COPD) (3). Specifically in the skin, in human psoriasis, both the number and activity of mast cells are increased in psoriatic lesions (4). We are therefore interested in delineating the roles of mast cell proteases in both homeostasis and in inflammatory situations in the skin, whilst also determining the role of TMT? both in vitro and in vivo.
Travel and Contact Information
Michael Smith Lecture Theatre
Michael Smith Building