Immune Regulation Research Group

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Research Focus

The main focus of this research is to define the functional properties and the regulation of a new class of immuno-regulatory receptors termed as Leukocyte immunoglobulin-like receptors (LIRs). In addition, the research aims to identify the, as yet unknown, ligands for these molecules. We and our collaborators in the US have recently published several high impact papers demonstrating that LIRs modulate cellular responses through immunoreceptor tyrosine-based inhibitory motifs, or via association with the Fc receptor  chain that contains immunoreceptor tyrosine-based activation motifs. We have also demonstrated that an imbalance in the expression of activating and inhibitory LIRs on leucocytes might be a key mechanism in the development of auto-immune diseases such as rheumatoid arthritis in humans. We currently are investigation the function of LIRs on the major cells that are involved in allergic inflammation. Identification and characterization of natural ligand(s) for these molecules is one of the major aims for an NHMRC funded Project grant awarded this year.

The assay systems used by the Group are based on human tissue, human primary cells and human cell lines, and include: flow cytometry, real time PCR, site-directed mutagenesis, ELISA for cytokines, histamine release, EDN assays, BioPlex, Western blot, immunoprecipitations, immunohistochemistry. As well as radioactive and non-radioactive ligand binding assays. In addition, expression of recombinant proteins in E-coli, baculovirus and mammalian systems is undertaken. Novel in vitro diferentiation systems have been developed for cord blood stem cells to generate human mast cells, myeloid cells and fibroblasts. Tandem mass spectrometry is used for identification of unknown protein ligands.

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Researchers

Dr Nicodemus Tedla, Senior Lecturer
Ainslie Mitchell, Research Assistant
Owen Huynh, PhD Student

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Selected Publications

Sloane DE, Tedla N, Awoniyi M, MacLashan DW, Borges L, Austen KF, Arm JP. Leukocyte Immunoglobulin-like Receptors: novel innate receptors for human basophil activation and inhibition. Blood, 2004, 104(9). 1-8. Tedla N, Bandeira-Melo C, Tassinari P, Sloane DE, Samplaski M, Cosman D, Borges L, Weller PF, Arm JP. Activation of human eosinophils through leukocyte immunoglobulin-like receptor 7. PNAS, 2003, 4:100(3):1174-9 Tedla N, Gibson K, McNeil HP, Cosman D, Borges L, Arm JP. The co-expression of activating and inhibitory leukocyte immunoglobulin-like receptors in rheumatoid synovium. Am J Pathol. 2002, 160: 425-431. Grimbaldeston MA, Geczy CL, Tedla N, Finlay-Jones JJ, Hart PH. S100A8 induction in keratinocytes by ultraviolet A irradiation is dependent on reactive oxygen intermediates. J Invest Dermatol. 2003, 121(5):1168-74 Tedla N, Wang H, McNeil HP, Di Girolamo N, Hampartzoumian T, Wakefield D, Lloyd AR. Regulation of T lymphocyte trafficking into lymph nodes during an immune response by the chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta. J Immunol. 1998, 161:5663-5672. Tedla N, Palladinetti P, Kumar RK, Chattophadhay, U, Kelly, MD, Digirolamo, N, Cooke, BE, Truskett, PG, Dwyer, JM., Wakefield, D, Lloyd, AR.. Chemokines and T cell recruitment to lymph nodes in HIV. AMJ Pathol. 1996, 148:1367-1373. Wang, H, Tedla, N, Lloyd, AR, Wakefield D, McNeil, HP. Mast cell activation and migration to lymph nodes during induction of an immune response in mice. J Clin Invest. 1998, 102(8):1617-26. Tedla N, Dwyer J, Truskett P, Taub D, Wakefield D, Lloyd A. Phenotypic and functional characterization of lymphocytes derived from normal and HIV-1-infected human lymph nodes. Clin Exp Immunol. 1999, 117(1):92-99 Wang H, McNeil HP, Husain A, Liu KH, Tedla N, Thomas PS, Raftery MJ, King GC, Cai ZY, Hunt JE.  Tryptase Is Expressed in Multiple Human Tissues, and a Recombinant Form Has Proteolytic Activity. J Immunol, 2002, 169:5145-5152. Tedla N, Palladinetti P, Wakefield D, Lloyd AR. Abundant expression of chemokines in malignant and infective human lymphadenopathies. Cytokine, 1999, 11(7): 531-40.