After injury, the immune system reacts with both a systemic pro-inflammatory and counter-inflammatory response, which results in the disruption of immune homeostasis. This leaves patients uniquely vulnerable to infections after injury, because the innate and adaptive arms of the immune system are less able to work in concert to fight off invading pathogens. Our lab studies the immune response to injury with the dual goals of a better understanding of these diverging immune responses and the identification of critical biomarkers and potential therapeutic targets, in order to protect patients from infection after injury. To accomplish this, we perform single-cell analysis using mass cytometry by time-of-flight (CyTOF) or flow cytometry to evaluate injury- or infection-induced phenotypic changes in immune cell populations. To study changes in immune function and homeostasis, we measure cytokines by Luminex bead assay in tissue extracts, plasma, and cytokine production by stimulated cells.
- Stoecklein VM, Osuka A, Lederer JA. Trauma equals danger–damage control by the immune system. Journal of Leukocyte Biology. 2012; 92(3):539-51.
- Osuka A, Hanschen M, Stoecklein V, Lederer JA. A protective role for inflammasome activation following injury. Shock. 2012; 37(1):47-55.
- O’Leary FM, Tajima G, Delisle AJ, Ikeda K, Dolan SM, Hanschen M, Mannick JA, Lederer JA. Injury-induced GR-1+ macrophage expansion and activation occurs independently of CD4 T-cell influence. 2011; 36(2):162-9.
- Hanschen M, Tajima G, O’Leary F, Ikeda K, Lederer JA. Injury induces early activation of T-cell receptor signaling pathways in CD4+ regulatory T cells. Shock. 2011; 35(3):252-7.
- MacConmara MP, Tajima G, O’Leary F, Delisle AJ, McKenna AM, Stallwood CG, Mannick JA, Lederer JA. Regulatory T cells suppress antigen-driven CD4 T cell reactivity following injury. Journal of Leukocyte Biology. 2011; 89(1):137-47.
Radiation and Radiation Combined Injury (RCI) Medical Countermeasure and Radiation Immunology Research
In the event of a nuclear disaster, people will be affected both by traumatic injury as well as radiation, which would create a different immune phenotype than in patients with just injury alone. Therefore, our lab uses animal models to study the changes in the immune system after radiation as well as in RCI to better understand the immunological effects of these insults. We use systems immunology technologies to evaluate changes in blood as well as in organs to better understand how infections develop after radiation and injury.
While trauma or radiation injury cannot necessarily be prevented, post-event immunotherapy could save lives by boosting the immune system at a critical time to prevent devastating infections. Our lab has a particular focus on CpG oligodeoxynucleotides (ODNs), which are immunostimulatory Toll-like receptor – 9 (TLR9) ligands, and their potential for use as post-injury immunotherapy for people exposed to radiation or radiation combined injury following a radionuclear event. We are also working on using specific CpG-ODN sequences as immunotherapy for traumatic injuries.
- Wanke-Jellinek L, Keegan JW, Dolan JW, Guo F, Chen J, Lederer JA. Beneficial effects of CpG-Oligodeoxynucleotide Treatment on Trauma and Secondary Lung Infection. Journal of Immunology. 2016; 196(2):767-77.
- Stoecklein VM, Osuka A, Ishikawa S, Lederer MR, Wanke-Jellinek L, Lederer JA. Radiation exposure induces inflammasome pathway activation in immune cells. Journal of Immunology. 2015; 194(3):1178-89.
- Tajima G, Delisle AJ, Hoang K, O’Leary FM, Ikeda K, Hanschen M, Stoecklein VM, Lederer JA. Immune system phenotyping of radiation and radiation combined injury in outbred mice. Radiation Research. 2013; 179(1):101-12.
FNIH Accelerating Medical Partnerships Autoimmune Disease Research
Autoimmune diseases such as lupus and rheumatoid arthritis are caused by an overactive immune response that leads the immune system to attack one’s own body. Better understanding of the cellular changes that lead to this misdirected response could revolutionize treatment of patients with these conditions. Through this multi-institutional project, we hope to understand what specific cell types are most implicated in these responses and potentially identify intervenable targets that could be used in the treatment of these conditions. To accomplish this we will be looking at peripheral total leukocytes and tissue resident cells.
- Rao, D.A., Gurish, M.F., Marshall, J.L., Slowikowski, K., Fonseka, C., Liu, Y., Donlin, L.T., Henderson, L.A., Wei, K., Mizoguchi, F., Teslovich, N.C., Weinblatt, M.E., Massarotti, E.M., Coblyn, J.S., Helfgott, S.M., Lee, Y.C., Todd, D.J., Bykerk, V.P., Goodman, S.M., Pernis, A.B., Ivashkiv, L.B., Karlson, E.W., Nigrovic, P.A., Filer, A., Buckley, C.D., Lederer, J.A., Raychaudhuri, S., Brenner, M.B. Pathologically expanded peripheral T helper subset drives B cells in rheumatoid arthritis. Nature, 2016 (in press).