The control of lymphatics in autoimmunity. (360G-Wellcome-081020_Z_06_Z)

£801,111

The immune system has evolved to defend the host from invading pathogens. This powerful system must be tightly regulated by inhibitory mechanisms. Failure of such regulatory mechanisms can result in autoimmunity. Following an infection, lymphocytes and antigen presenting cells are trafficked from sites of inflammation by a network of lymphatic vessels into draining lymph nodes. The lymph node and lymphatic vasculature subsequently expand to facilitate the immune response. Recent evidence su ggests that B cells and macrophages play a critical role in this process through the production of lymphangiogenic factors such as VEGF-A and VEGF-C. Many autoimmune diseases are characterised by defective immune inhibition and B cell hyperactivity. I propose to determine how deficiency of inhibitory receptors affects lymphangiogenesis and the development of autoimmunity, and whether inhibition of lymphangiogenesis might prevent or treat autoimmune disease. I intend to study the production of lymphangiogenic factors in vitro by B cells and macrophages isolated from mice with defective immune inhibition, and by human B cells and macrophages with dysfunctional inhibitory receptors or from patients with autoimmune disease. I will also investigate lymphangiogenesis in autoimmune-prone mice in vivo and develop novel mouse models and imaging techniques to characterize lymphangiogenesis and lymphatic-leukocyte interactions in autoimmunity.

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Grant Details

Amount Awarded 801111
Applicant Surname Clatworthy
Approval Committee Clinical Interview Committee
Award Date 2006-12-07T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Intermediate Clinical Fellowship
Internal ID 081020/Z/06/Z
Lead Applicant Prof Menna Clatworthy
Partnership Value 801111
Planned Dates: End Date 2013-02-28T00:00:00+00:00
Planned Dates: Start Date 2007-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Dr Ulrich Von Andrian, Prof Ken Smith