Regulation of monocyte function by iNKT cells in normal subjects and sarcoidosis. (360G-Wellcome-094049_Z_10_Z)

Invariant NKT cells are a unique subset of immuneregulatory cells, able to prevent expansion of antigen-specific T cells. I hypothesise that iNKT cells influence the proliferation and function of monocytes, and that defects in this control pathway in conditions like sarcoidosis (where there is a lack of iNKT cells), results in abnormally activated pro-inflammatory macrophages and granulomagenesis. The effects of iNKT cells on monocytes in normal individuals will be studied by examining the e ffect of iNKT clones on monocyte function. Monocytes will be co-cultured with iNKT cells or control, after which I will examine the impact of iNKT cells on monocytic (i) phagocytic ability (ii) phenotypic changes (iii) ability to stimulate T cell proliferation and (iv) global gene expression post LPS stimulation I will also study monocyte phenotype and function in sarcoidosis patients compared to controls (healthy and other respiratory disease) by examining (i) IL-10 and TNF-alpha secretion ( ii) markers of monocyte differentiation (iii) phagocytosis capacity and (iv) differentiation after LPS stimulation. The work will contribute to research in regulation of monocyte function, improve understanding of disease mechanisms in sarcoidosis, and provide a platform for potential immune cellular therapeutic intervention.