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You searched for subject:(LILRB4). Showing records 1 – 2 of 2 total matches.

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University of New South Wales

1. Lu, Hao Kim. Mechanism of the inhibitory effects of leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytes.

Degree: Medical Sciences, 2011, University of New South Wales

The leukocyte immunoglobulin-like receptor (LILR) B4 belongs to a family of activating and inhibitory cell surface receptors that are increasingly recognised as key regulators of leukocyte functions. LILRB4 is an inhibitory molecule that is highly expressed on the surface of monocytes and macrophages. It is believed to inhibit leukocyte activation through the recruitment of phosphatases to its ITIM-containing cytoplasmic tail. However, there is no comprehensive data that elucidate the underlying mechanisms of LILRB4-mediated inhibitory effects and signalling in vitro and in vivo. This is in part due to lack of in depth investigation of the effects of LILRB4 in vitro.The first part of the project showed that LILRB4 is a potent inhibitor of FcγRI-mediated TNFα production in monocyte. Furthermore, LILRB4 was shown to selectively down-regulate key protein tyrosine kinases such Lck, Syk, LAT and Erk that are involved in the secretory functions of monocytes, but not the cytoskeletal protein α-actinin-4. Furthermore, this study is the first to shows that LILRB4 utilise multiple phosphatases including a novel SHP-1-like phosphatase for its inhibitory functions.The second part of this project investigated whether LILRB4 also modulate other key monocyte/macrophage functions, notably Fc receptor-mediated phagocytosis and bactericidal activity. While LILRB4 is a potent inhibitor of FcγRI-mediated pro-inflammatory cytokine production, the results in this chapter show that it has only limited effect on phagocytosis and bactericidal functions, indicating that it is a selective inhibitory receptor of the secretory functions of monocytes.Finally, the last part of this project focused on the development of novel methodologies for the identification and characterisation of LILRB4 ligand(s). Using a recombinant LILRB4 protein generated from a mammalian cell system, this chapter shows that the ligand(s) of LILRB4 is expressed on the surface of PBMCs from healthy individuals. For the first time, the dissociation constant (Kd) of this interaction was also determined to be 29 nM, indicating a moderately high affinity receptor-ligand interactions between LILRB4 and its ligand(s).Taken together, this work demonstrated that LILRB4 is a potent yet selective inhibitor of key monocyte functions and has provided some preliminary data on the characteristics of the natural ligand(s) of LILRB4. Advisors/Committee Members: Tedla, Nicodemus, Medical Sciences, Faculty of Medicine, UNSW, Bryant, Katherine, Medical Sciences, Faculty of Medicine, UNSW.

Subjects/Keywords: Monocytes; LILRB4; Signalling; Cytokines; Ligands

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Lu, H. K. (2011). Mechanism of the inhibitory effects of leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytes. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/51613 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10280/SOURCE02?view=true

Chicago Manual of Style (16th Edition):

Lu, Hao Kim. “Mechanism of the inhibitory effects of leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytes.” 2011. Doctoral Dissertation, University of New South Wales. Accessed October 17, 2019. http://handle.unsw.edu.au/1959.4/51613 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10280/SOURCE02?view=true.

MLA Handbook (7th Edition):

Lu, Hao Kim. “Mechanism of the inhibitory effects of leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytes.” 2011. Web. 17 Oct 2019.

Vancouver:

Lu HK. Mechanism of the inhibitory effects of leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytes. [Internet] [Doctoral dissertation]. University of New South Wales; 2011. [cited 2019 Oct 17]. Available from: http://handle.unsw.edu.au/1959.4/51613 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10280/SOURCE02?view=true.

Council of Science Editors:

Lu HK. Mechanism of the inhibitory effects of leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytes. [Doctoral Dissertation]. University of New South Wales; 2011. Available from: http://handle.unsw.edu.au/1959.4/51613 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10280/SOURCE02?view=true


University of New South Wales

2. Park, Mijeong. Regulation of monocyte/macrophage activation by Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4).

Degree: Medical Sciences, 2016, University of New South Wales

The leukocyte immunoglobulin-like receptor B4 (LILRB4) belongs to a family of cell surface receptors, primarily expressed on mono-myeloid cells. LILRB4 has been shown to inhibit FcγRI-mediated pro-inflammatory cytokine production by monocytes and induce tolerogenic dendritic cells in vitro. It is believed that LILRB4 regulates monocyte/macrophage activation through its three intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) by paring with activating receptor, bearing ITAM, and by dephosphorylation of non-receptor tyrosine kinases via recruitment of Src homology phosphatase-1 (SHP-1). However, the exact mechanism and the functions depending on its structure and stimuli are still unclear. In addition, regulatory functions of LILRB4 paring with non-ITAM associated activating receptors, including TLR4 is less researched. Thus, this thesis investigates, for the first time, the functions of LILRB4 in regulation of monocyte/macrophage activation depending on the position of the tyrosine residues of its ITIMs, and stimuli.Here it is shown for the first time that LILRB4 is a complex immuno-regulatory receptor that exerts dual inhibitory and activating functions in FcγRI and/or TLR4-mediated monocyte/macrophage activation including receptor-ligand internalisation, endocytosis, cytokine production, phagocytosis and bactericidal activity. Most importantly, each ITIM of LILRB4 has a different function in monocyte/macrophage activation depending on the position of its tyrosine residue. Thus, the tight regulation of these ITAM-containing and non-ITAM receptors by each LILRB4 ITIM may play a key role in fine-tuning immune responses. In addition, the results for the regulatory function of LILRB4 using various ITIM mutants in response to different stimuli provide better understanding of the signalling pathways of LILRB4 that may contribute to use LILRB4 as a potential therapeutic agent for an appropriate immune response using selective LILRB4 ITIM/s. Although no LILRB4 ligand is identified, new methodologies and the potential candidate ligands of LILRB4 which are provided here may contribute to identifying the nature of LILRB4 ligand/s in the near future. Advisors/Committee Members: Tedla, Nicodemus, Medical Sciences, Faculty of Medicine, UNSW, Thomas, Paul, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW.

Subjects/Keywords: FcγRI and/or TLR4-mediated monocyte/macrophage activation; Leukocyte immunoglobulin-like receptor B4 (LILRB4); Intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs); The nature of LILRB4 ligand/s; Receptor-ligand internalisation, endocytosis, cytokine production, phagocytosis and bactericidal activity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Park, M. (2016). Regulation of monocyte/macrophage activation by Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4). (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/56736 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41255/SOURCE02?view=true

Chicago Manual of Style (16th Edition):

Park, Mijeong. “Regulation of monocyte/macrophage activation by Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4).” 2016. Doctoral Dissertation, University of New South Wales. Accessed October 17, 2019. http://handle.unsw.edu.au/1959.4/56736 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41255/SOURCE02?view=true.

MLA Handbook (7th Edition):

Park, Mijeong. “Regulation of monocyte/macrophage activation by Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4).” 2016. Web. 17 Oct 2019.

Vancouver:

Park M. Regulation of monocyte/macrophage activation by Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4). [Internet] [Doctoral dissertation]. University of New South Wales; 2016. [cited 2019 Oct 17]. Available from: http://handle.unsw.edu.au/1959.4/56736 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41255/SOURCE02?view=true.

Council of Science Editors:

Park M. Regulation of monocyte/macrophage activation by Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4). [Doctoral Dissertation]. University of New South Wales; 2016. Available from: http://handle.unsw.edu.au/1959.4/56736 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41255/SOURCE02?view=true

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