Each of us relies on the immune system to guard the body against invasion by harmful agents. Cells of the immune system arise from stem cells that progressively change and develop into the many different mature cell types. Once mature, each cell type can be activated by detection of foreign material and to play a highly specialized role in immunity. Detection of a pathogen also leads to extensive communication amongst the many cell types that strongly influence the outcome of the immune response.

In the Immune Cell Research laboratory we are particularly interested in the fascinating immune cell type-the dendritic cells (DC). DC are bone marrow derived cells. They are the most efficient antigen presenting cells. DC play important roles in either initiating antigen specific immune responses against pathogens or inducing immune tolerance to self-antigens. DC are heterogeneous and contain phenotypically and functionally distinct subpopulations. We are interested in how the development of these DC populations is regulated by various molecules, including cytokines, transcription factors and microRNAs. These studies are crucial for revealing the mechanisms underlying the development of autoimmune diseases.

1. Molecular regulation of immune cell lineage commitment and differentiation from heamatopoietic stem and progenitor cells

2. Regulation of development and functions of the mucosal dendritic cell, macrophage and other innate immune cells

3. The effects of intestinal microbiota on the differentiation of immune cells

4. The mechanisms of altered innate immune cell development and function in the development of immune related diseases.

1997 Cancer Research Institute (New York) Clinical

Investigator Award for Cancer Immunology

1996 Burnet Prize for Outstanding Young Scientists

1. Guo XH, Wu N, Shang YL，Liu X, Wu T, Zhou YF, Liu X, Huang JY, Liao XB andWu L.The novel Toll-like receptor 2 agonist sUP3 enhances antigen Presentation and T cell activation by Dendritic cells.Front. Immunol. 8:158. doi: 10.3389/fimmu. 2017.00158.

2. Zhou, H., Xiao, J., Wu, N., Liu, C., Xu, J., Liu, F., &Wu, L.MicroRNA-223 Regulates the Differentiation and Function of Intestinal Dendritic Cells and Macrophages by Targeting C/EBPβ.Cell Reports2015; 13(6), 1149-1160.

3.XiaoJ,ZhouHBandWuL.The non-canonical Wnt pathway negatively regulates the dendritic cell development by inhibiting the expansion of Flt3+lymphocyte-primed multipotent precursors.Cell & Mol. Immunol.2015 Jun 8. doi: 10.1038/cmi.2015.39. [Epub ahead of print]

4.Carotta S., Dakic A., D’Amico A., Pang SHM., Greig KT, Nutt SL and Wu L. The Transcription Factor PU.1 Controls Dendritic Cell Development and Flt3 Cytokine Receptor Expression in a Dose Dependent Manner.Immunity. 2010; 28:628-41.

5. Wu L. A Flt3L Encounter: mTOR Signaling in Dendritic Cells (Preview).Immunity.2010, 33:580-582.

6. Proietto AI, van Dommelen S, Zhou P, Rizzitelli A, D'Amico A, Steptoe RJ, Naik SH, Lahoud MH, Liu Y, Zheng P, Shortman K and Wu L. Dendritic cells in the thymus contribute to T-regulatory cell induction.ProcNatlAcadSci.USA. 2008; 105:19869-19874.

7. Naik SH, Sathe P, Park HY, Metcalf D, Proietto AI, Dakic A, Carotta S, O'Keeffe M, Bahlo M, Papenfuss A, Kwak JY, Wu L, Shortman K. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo.NatureImmunology. 2007; 8:1217-26.

8. Wu L, Liu YJ. Development of dendritic-cell lineages.Immunity. 2007; 26:741-50.

9. Naik SH, Metcalf D, van Nieuwenhuijze A, Wicks I, Wu L, O'Keeffe M, Shortman K. Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes.NatureImmunology. 2006; 7:663-71.

10. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE. Generation of a functional mammary gland from a single stem cell.Nature. 2006; 439:84-88.

11. Dakic A, Metcalf D, Di Rago L, Mifsud S, Wu L*, Nutt SL* (equal last author). PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis.JExpMed. 2005; 20:1487-502.

12. Nutt SL, Metcalf D, D'Amico A, Polli M, Wu L. Dynamic regulation of PU.1 expression in multipotent hematopoietic progenitors.JExpMed. 2005; 201:221-231.

13. D’Amico A and Wu L. The Early Progenitors of Mouse Dendritic Cells and Plasmacytoid pre-Dendritic Cells are within the Bone Marrow Hemopoietic Precursors Expressing Flt3.J.Exp.Med. 2003;198:293-303.

14. Wu L, D'Amico A, Hochrein H, O’Keeffe M, Shortman K and Lucas K. Development of thymic and splenic dendritic cell populations from different hemopoietic precursors.Blood2001; 98:3376-33 82.

15. Wu L, D’Amico A, Winkel K.D, Suter M, Lo D, Shortman K. RelB is essential for the development of Myeloid-related CD8- dendritic cells but not of lymphoid-related CD8+ dendritic cells.Immunity1998; 9:839-847.

16. Wu L, Nichogainnopoulou A, Shortman K, Georgopoulos K. Cell autonomous defects in dendritic cell populations of ikaros mutant mice point to a developmental relationship with the lymphoid lineage.Immunity1997; 7:483-492.

17. Wu L, Li C-L, Shortman K. Thymic dendritic cell precursors: relationship to the T-lymphocyte lineage and phenotype of the dendritic cell progeny.J.Exp.Med. 1996; 184:903-911.

18. Ardavin C, Wu L, Li C-L, Shortman K. Thymic dendritic cells and T cells develop simultaneously within the thymus from a common precursor population.Nature1993; 362: 761-763.

19. Wu L, Antica M, Johnson GR, Scollay R, Shortman K. Developmental potential of the earliest precursor cells from the adult mouse thymus.JExpMed. 1991; 174: 1617-1627.

20. Wu L, Scollay R, Egerton M, Pearse M, Spangrude GJ, Shortman K. CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus.Nature1991; 349: 71-74.