MCCIR AZ/GSK Update Seminar Series
Dates: | 2 March 2015 |
Times: | 15:30 - 16:30 |
What is it: | Seminar |
Organiser: | Manchester Collaborative Centre for Inflammation Research |
Who is it for: | University staff |
Speaker: | Gloria López-Castejón, A. E. Saunders |
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Negative regulation of the skin immune system in health and disease - A. E. Saunders
The balance between tolerance and immunity is important throughout the body. At barrier sites this balance must be particularly tightly controlled, as immune cells must be poised to respond to invading pathogens whilst remaining tolerant to commensal microbes and other environmental stimuli.
I have a particular interest in mechanisms that actively signal to maintain immune cell tolerance in the skin. One such mechanism involves CD200R and its ligand, CD200. In the skin CD200 is expressed in the stem-like cells in the bulge region of hair follicles whereas CD200R is expressed by a variety of immune cells particularly those of the myeloid lineage. Signalling via this pathway has previously been shown to suppress alloreactivity in the skin and allergic and viral responses in other organs. I am investigating if this pathway plays a role in skin immune system homeostasis or the chronic inflammatory skin disease, psoriasis. I have demonstrated that CD200 is expressed at lower levels in uninvolved psoriatic skin compared to healthy skin, and I have found that CD200R signalling suppresses skin inflammation in the Aldara cream model in mice. I am now determining the cell types and mechanism involved in the regulation of skin inflammation by CD200R.
I have also observed CD200R expression on mouse and human skin innate lymphoid cells and we are currently investigating the effects of CD200R signaling on innate lymphoid cell function.
Understanding this pathway will deepen our knowledge of the immune system in the skin and may aid the development of novel therapeutics to treat inflammatory skin disease.
Trimming ubiquitin to control inflammatory responses - Gloria López-Castejón
Deubiquitilases (DUBs) are proteases that remove or edit ubiquitin chains from target proteins. They are crucial to maintain cellular homeostasis and play very important roles in the immune system were they are required for the correct functioning of inflammatory signalling cascades. Despite this, it is still largely unknown how DUBs expression is regulated in immune cells as well as what their role and mechanisms of action are. My research focuses in understanding new roles for DUBs in macrophages given the importance of these immune cells in sensing danger signals to initiate inflammation.
We have so far identified novel transcriptionally regulation of DUBs by TLR activation. These have been identified after an RNA-seq analysis in human THP1 cells and further validation in human derived macrophages. Further work is ongoing to investigate the relevance of this observation.
In addition we have observed that inhibition of the deubiquitilase USP7 with P22077 impairs inflammasome activation in human derived macrophages and monocytes. P22077 blocks the release of IL-1B and IL-18 and the cell death associated to inflammasome activation. This impairment is independent of transcriptional regulation of the inflammasome and USP7. In addition we show that this effect is not caused by lysosomal pathway interference. Although more experiments are required to further confirm the involvement of USP7 and understand the mechanistic insights of this process, this data shows a novel DUB involved in the assembly of the inflammasome complex.
Speakers
Gloria López-Castejón
Organisation: Faculty of Life Sciences
A. E. Saunders
Organisation: Faculty of Life Sciences
Travel and Contact Information
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Michael Smith Lecture Theatre
Michael Smith Building
Manchester