The role of resident memory T cells in barrier immunity and autoimmune disease
Infections are commonly acquired through barrier tissues such as the skin, gut and lung, hence establishing memory CD8+ killer T cell populations at these sites is critical for effective immune protection. While most memory T cells circulate in the blood, a distinct lineage, termed tissue-resident memory T cells (Trm), resides and remains in peripheral tissues. Laura’s group’s work has shown that these cells form a defensive barrier providing immediate local control of viral infection. Using methods including flow cytometry, histology and intravital 2-photon microscopy, current work focuses on how Trm cells respond following secondary infection, and they are developing novel strategies to boost Trm cell responses, which aim to facilitate the development of strategies to exploit these cells in vaccination settings. Work in the laboratory also aims to understand the role of Trm cells in autoimmune conditions such as psoriasis, and Laura’s group is investigating new approaches to eliminate pathological cells from peripheral tissues.
Understanding the regulation of tissue-resident memory T cell development
Laura’s group’s work has shown that tissue-resident memory T cells (Trm) are phenotypically and functionally distinct to memory T cells in the circulation. They have found that Trm development is a multistep process that requires the action of several molecules, and that these cells acquire a unique transcriptional profile during their differentiation. Using several different infectious models including Influenza, herpes simplex virus, Listeria and LCMV, Laura’s group is investigating the regulatory cues and mechanisms that govern Trm cell development in different tissues, with a focus on the transcriptional networks that regulate commitment to this immune cell lineage.
Identifying the mechanisms of immune cell development in peripheral tissues
It is now clear that ‘tissue residency’ extends past the T cell lineage, and that various immune cell populations including innate lymphoid cells (ILC) and NKT cells, can persist long-term in peripheral tissues. Laura’s group is interested in the role of the tissue microenvironment in shaping these immune cell populations, and are studying the tissue-tropic factors and signals that govern the environmental adaptation of immune cells to different tissues. Their work also investigates common mechanisms that are required to establish tissue residency such as the shutdown of tissue egress, and they are deciphering novel factors required for these processes. Their goal is to provide a molecular framework for tissue-resident lymphocyte differentiation, which will provide a basis for targeting these cells in future immune cell-based therapies.
Dr Laura Mackay is a laboratory head and senior lecturer at the University of Melbourne. She is a Howard Hughes Medical Institute (HHMI) – Gates International Scholar, NHMRC Career Development Fellow, recipient of the Victorian Young Tall Poppy Science Award, serves on the council of the Australian Society for Immunology and holds an Adjunct Professor appointment at the Singapore Immunology Network (SIgN), A*STAR. Laura obtained her PhD from the University of Birmingham, UK, in 2009, before taking up a postdoctoral position with Professor Francis Carbone (University of Melbourne). With grant support from the NHMRC and ARC, Laura established an independent group at the Peter Doherty Institute in 2015. Her laboratory studies cellular immune responses, with a focus on the genes and signals that control resident memory T cell differentiation, with a view to harness these cells to develop new treatments against infection, cancer, and autoimmune disease.