Wayne Yokoyama, MD
In studies directly related to Rheumatology patients, we have initiated studies on patients with Kawasaki disease. With our collaborators, we are studying these patients who present as children having high fevers, and muco-cutaneous lymph node syndrome. They often have vasculitis and aneurysms, particularly of the coronary arteries. It is more prevalent in children of Asian descent, suggesting a genetic predisposition. We are currently exploring this possibility with state-of-the-art technologies.
In addition, we are continuing our long-term investigations of the innate immune system which defends the host from pathogens and cancer while the adaptive immune system is being mustered. By providing early detection and control, it can also shape the T and B cell response. Our major focus is on understanding the functions of natural killer (NK) cells which constitute a major constituent of the innate immune system. We are particularly interested in NK cell receptors that recognize ligands on their infected or tumor cell targets. Over the years, we have identified and characterized NK cell inhibitory receptors that recognize major histocompatibility complex class I molecules on the target cell. These inhibitory receptors block the function of NK cell activation receptors that recognize other target cell surface ligands, including molecules encoded by viruses. Together, the NK cell receptors dictate whether or not the NK cell will kill normal or diseased cells. We also showed they have other effects on NK cell function, i.e., tolerance, which also includes a recently described process termed “licensing” and “anergy” due to engagement of ligands expressed on self-tissues by inhibitory or activation receptors, respectively. Recently, we determined that certain tissues, such as the liver, contain two distinct populations of NK cells, those that re-circulate throughout the body, and tissue-resident NK cells that reside in tissues. We are currently exploring the functions of these major NK cell subsets.
Finally, our work on the role of NK cells in anti-pathogen defense has led to studies of immune responses to large DNA viruses, MCMV and CPXV. We are especially interested in how these viruses interact with the host, since much of their genomes is dispensable for in vitro growth and replication, i.e, they encode molecules that modulate the immune system. MCMV and CPXV are amenable for such analyses since their natural reservoirs are rodents and thus, immunopathogenesis studies in mice are applicable to host-pathogen interactions.
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- Sojka, D.K., Plougastel-Douglas, B., Yang, L., Pak-Wittel, M.A., Artyomov, M.N., Ivanova, Y., Zhong, C., Chase, J.M., Rothman, P.B., Yu, J., Riley, J.K., Zhu, J., Tian, Z., and Yokoyama, W.M. Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells. eLife 2014; 3:e01659. PMCID: PMC3975579
- Littman, D.R., and Yokoyama, W.M. (Eds.) Annual Review of Immunology Vol. 32, Annual Reviews, Inc. Palo Alto, 2014, 726 pp
- Yokoyama, W.M., Sojka, D.K., Peng, H., and Tian, Z. Tissue-resident natural killer cells. Cold Spring Harbor Symposia on Quantitative Biology: Immunity & Tolerance 2014; 78, in press.
- Ebihara, E., Jonsson, A.H., and Yokoyama, W.M. NK cell licensing in mice with inducible expression of MHC class I. Proc Natl Acad Sci (USA) 2013; E4232-E4237. PMCID: PMC3831452
- Fogel, L.A., Yokoyama, W.M., and French, A.R. Natural killer cells in human autoimmune disorders. Arth Res Ther 2013; 15:216-225. PMCID: PMC3979027
- Pak-Wittel, M.A., Yang, L., Sojka, D.K., Rivenbark, J.G., and Yokoyama, W.M. Interferon- mediates chemokine-dependent recruitment of natural killer cells during viral infection. Proc Natl Acad Sci (USA) 2013;110:E50-9. PMCID: PMC3538256
- Peng, H., Jiang, X., Chen, Y., Sojka, D.K., Wei, H., Gao, X., Sun, R., Yokoyama, W.M., and Tian, Z. CD49a+ DX5– NK cells are liver-resident NK cells that confer adaptive immunity in skin-contact inflammation. J Clin Invest 2013;123:1444-1456. PMCID: PMC3613925.
- Gainey, M.D., Rivenbark, J.G., Cho, H., Yang, L., and Yokoyama, W.M. Viral MHC class I inhibition evades CD8+ T cell effector responses in vivo but not CD8+ T cell priming. Proc Natl Acad Sci (USA) 2012; 109:E3620-3267. PMCID: PMC3511129.
- Choi T, Ferris ST, Matsumoto N, Poursine-Laurent J and Yokoyama WM. Ly49-dependent NK cell licensing and effector inhibition involve the same interaction site on MHC ligands. J Immunol 2011 186: 3911-3917. PMCID: PMC3082152