Yong-Jun Liu, M.D., Ph.D.

1984, Norman Bethune University
1989, University of Birmingham, UK

UT M. D. Anderson Cancer Center
Immunology

Research Interests: Innate immunity; dendritic cell biology; T cell biology; cytokine biology; vaccine for cancers and viral infectious diseases

Dendritic cell development. My lab identified and purified the human plasmacytoid dendritic cell precursors (pDC), also known as type 1 IFN-producing cells (IPCs). We have demonstrated that pDC/IPCs are the key effector cells in anti-viral innate immunity and have the capacity to differentiate into mature DCs after activation. We have recently mapped the differentiation pathway of IPCs from human CD34+ early stem cells and shown that FLT3-ligand promotes IPC development from stem cells. We are currently investigating the function of other hematopoietic growth factors and stromal cells in IPC development, and determining the lineage origin of IPCs.

Pre-DC2/IPCs in HIV. We have recently shown that pDC/IPCs express CD4, CXCR4 and CCR5. Depletion of peripheral blood pre-DC2/IPCs associates with disease progression to AIDS in HIV injected subjects. While many viruses such as flu, HSV and Sandai induce pre-DC2/IPCs to produce large amounts of IFN-a, HIVs do not. We are currently investigating: i) What happens to pre-DC2/PICs after binding HIV? ii) Are pre-DC2/IPCs infected in HIV infected subjects? iii) Do pre-DC2/IPCs play a role in control HIV replication?

Expression and function of Toll-like recept on DC subsets. Our lab has recently shown that human subsets of human DC precursors express different sets of Toll-like receptors. While monocytes (pre-DC1) express TLR-1, 2, 4, 5, 6 and u, pre-DC2 preferentially express TLR-7 and 9. The expression of TLR-2 and 4 confer the ability of pre-DC1 to respond to the bacteria ligand for TLR-2 (PGN, LT, LP) and for TLR-4 (LPS) by producing large amounts of TNF-a, IL-6 and IL-12. The expression of TLR-9 confers the ability of pre-DC2 to respond to CpG ODN by producing large amounts of IFN-a. We are currently investigating how each of the TLR signaling to DC-precursors will determine the T cell polarizing function of DCs upon DC maturation.

Human TSLP. We have shown that human thymic stromal lymphopoietin (TSLP), a novel IL-7 like cytokine, potently activated CD11c+ dendritic cells and induced production of Ta-2 attracting chemokines TARC and MDC. TSLP-activated DCs primed naive T helper cells to produce pro-allertic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor necrosis factor-a, while down-regulating IL-10 and interferon-g. TSLP was highly expressed by epithelial cells, especially keratinocytes of atopic dermatitis. TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role of epithelial cells and dendritic cells in initiating allergic inflammation. We are currently investigating the function of TSLP-DCs in priming CD8 T cells and in regulating T cell homeostasis.

A tutorial in my laboratory will provide training in basic and advanced knowledge about the regulation of innate and adaptive immunity, and experimental experiences in isolation and characterization of human DC subsets, generation of human DC from hematopoietic stem cells, interaction between DCs and T cells.
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Siegal FB, Kadowaki N, Shodell M, Shodell M, Fitzerald-Bocarsly PA, Shah K, Ho S, Antonenko K, Liu Y-J (1999) The nature of the principal type 1 interferon-producing cells in human blood. Science 284:1835-1837.

Liu YJ (1999) Reciprocal control of T helper cell and dendritic cell differentiation. Science 283:1182-1186.

Kadowaki K, Antonenko S, Lau L, Liu YU (2000) Linking innate and adaptive immunity by natural interferon-a/b-producing cells. J Exp Med 192:227-236.

Blom B, Ho S, Antonenco S, Liu Y-J (2000) Generatio of IFN-a producing pre-DC2 from human CD34+ hematopoietic stem cells. J ExpMed 192:1785-1795.

Kadowaki N, Antomenko S, Ho S, Rissoan MC, Soumelis V, Porcelli SA, Lanier LL, Liu Y-J (2001) Distinct cytokine profiles of neonatal natural killer T cells after expansion with subsets of dendritic cells. J Exp med 193:1221-1226.

Liu Y-J (2001) Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell 106:259-262.

Soumelis V, Scotts I, Gheyas F, Bouhour D, Cozon G, Cotte L, Huang L, Levy J, Liu Y-J (2001) Depletion of natural interferon-alpha producing cells in AIDS patients. Blood 98:906-912.

Kadowaki K, Ho S, Antonenko S, de Waal Malefyt R, Dastelein RA, Bazan F, Liu Y-J (2001) Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J Exp Med 194:863-869.

Gilliet M, Liu Y-J (2002) Generation of human CD8 T suppressor cells with CD40- ligand activated lymphoid dendritic cells. J Exp Med 195:695-704.

Shortman K, Liu Y-J (2002) The development and function of human and mouse dendritic cell subtypes. Nature Immunol Rev 2:151-161.

Gilliet M, Boonstra A, Antonenko S, Paturel C, Trinchieri G, O'Garra A, Liu Y-J (2002) The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and GM-CSF. J Exp Med 195:953-958.

Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, Gilliet M, Ho S, Antonenko S, Lauerma A, Smith K, Gorman D, Zurawski S, Abrams, J, Menon S, McClanahan T, de Waal-Malefy R, Bazan F, Kastelein RA, Liu Y-J (2002) Human epithelial cells trigger dendritic cell-mediated allergic infmallation by producint TSLP. Nature Immunol 3:673-680.

Program Affiliation:
Program in Immunology