The leukocyte immunoglobulin like receptors (LILRs) are a group of receptors with immunomodulatory effects. Group 1 LILRs comprise of LILRB1, among others, and bind to class 1 MHC molecules and transmits inhibitory signals. Studies have shown that LILRB1 ligation during the monocyte differentiation process into dendritic cells (DCs) results in the generation of a population of cells that are tolerogenic. Here we hypothesize that this tolerogenic nature of the resultant cells is due to the high expression of nuclear factor kappa – light chain enhancer of activated B cells (NF-κB) inhibitor – A20 binding inhibitor of NF-κB signalling 1 (ABIN1). In this study we analyzed the effect that ABIN1 exerts on the maturation of DCs and CD14+HLA-DRlow/- monocytes - a population of cells that have been recently been identified as myeloid derived suppressor cells (MDSCs) in humans. LILRB1 ligated DCs and CD14+HLA-DRlow/- monocytes, when treated with ABIN1 siRNA, displayed an increase in the expression of antigen presentation and co-stimulatory molecules such as CD80, CD86, HLA-DR and HLA-ABC and displayed a greater capacity to produce cytokines like IL-12 and IFN-α. Additionally, they displayed a greater capacity to stimulate the adaptive component of the immune system in terms of IFN-γ production, cell proliferation and adapter molecule and mitogen activated protein kinase (MAPK) activation in T cells. Based on the results we obtained, it can be concluded that ABIN1 plays a significant role in maintaining the immature and suppressive phenotype of immature myeloid cells (IMCs) by dampening NF-κB signalling, while also exerting a negative effect on antiviral signalling.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:589494 |
| Date | January 2013 |
| Creators | Khanolkar, Rahul Chaitanya |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=202767 |
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