Microbiome, Infection, Immunity and Inflammation |
Our research program to define functional biology of a family of immune regulatory molecules, known as Leukocyte Immunoglobulin-like Receptors (LILRs) in innate immune responses, chronic inflammatory diseases and central nervous system injuries. A disproportionate response in magnitude and duration is detrimental to the host such as in autoimmune diseases and excessive inflammation after sepsis and reperfusion injuries of the CNS and heart. We identified a new family of receptors called Leukocyte Immunoglobulin-like Receptors that act in pairs to maintain the delicate balance between the extremes of reactivity and quiescence of the immune system. We are the first to describe their role in autoimmune diseases such rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and in post-stroke inflammation.
Current projects
Our present two research focuses are: 1) Development of LILRs as a new class of biological agents to treat neutrophil driven tissue injury including post-stroke and post-myocardial infarction acute inflammation and post-sepsis acute lung injury; 2) The interplay between gut microbiome, LILRs and HLA-B27 in the pathogenesis of HLA-B27-associated diseases, particularly HLA-B27-associated recurrent acute anterior uveitis.
- The role of leukocyte immunoglobulin-like receptors (LILRs) in modulation of innate immune responses in health and diseases such as autoimmunity.
- Development of a new class of anti-inflammatory biologic agents for the treatment of neutrophil driven tissue injury including post sepsis acute lung injury, and reperfusion injury after myocardial or cerebral infarction.
- HLA-B27 driven alteration of gut microbiome leading to HLA-B27 associated autoimmune diseases in humanized transgenic rats.
- Prospective cohort Longitudinal gut microbiota study in patients with HLA-B27 associated acute anterior uveitis and define underlying mechanisms.
- Fc-receptor mediated regulation of viral and bacterial infections and counter regulation by inhibitory LILRs.
Highlighted publications
- Activation of human eosinophils through leukocyte immunoglobulin-like receptor 7. Proceedings of the National Academy of Sciences 100 (3), 1174-1179. 10.1073/pnas.0337567100
- The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies. Trends in Microbiology 31 (2), 142-158. https://doi.org/10.1016/j.tim.2022.08.008
- Horizontal gene transfer and endogenous retroviruses as mechanisms for molecular mimicry. The Lancet Microbe 5 (1), e4-e5 https://doi.org/10.1016/S2666-5247(23)00316-6
- Soluble LILRA3, a potential natural anti-inflammatory protein, is increased in patients with rheumatoid arthritis and is tightly regulated by interleukin 10, tumor necrosis alpha and interferon gamma. The Journal of rheumatology 37 (8), 1596-160 https://doi.org/10.3899/jrheum.091119
- Soluble LILRA3 promotes neurite outgrowth and synapses formation through a high-affinity interaction with Nogo 66. Journal of cell science 129 (6), 1198-1209. https://doi.org/10.1242/jcs.182006
- Nuclear leukocyte immunoglobulin-like receptor A3 is monomeric and is involved in multiple layers of regulated gene expression and translation. Journal of Proteome Research 20 (6), 3078-3089. https://doi.org/10.1021/acs.jproteome.0c00946
Our experts
Team members
- Dr Fernando Santiago
- Dr Rohit Parthasarathy
- Ms. Prakruti Sirigeri
Associated academics
- Professor Rowena Bull
- Professor Andrew Lloyd
- A/Professor Nadeem Kaakoush
- Professor Denis Wakefield
- A/Professor Cristan Herbert
- Professor Paul Thomas
- A/Professor Chaturaka Rodrigo
Research Theme