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