Associate Scientist, Autoimmunity and Inflammation Program and Pediatric Rheumatology, Hospital for Special Surgery
Associate Professor, Department of Microbiology and Immunology, Weill Medical College of Cornell University
Associate Professor, Graduate Program in Immunology and Microbial Pathogenesis, Weill Medical College of Cornell University
BS Yale University
MD, PhD Yale University
Pediatrics, Children’s Hospital of Philadelphia
Pediatric Rheumatology, University of California, San Francisco
Webster B, Ekland EH, Agle LM, Chyou S, Ruggieri R, Lu TT. Regulation of lymph node vascular growth by dendritic cells. Journal of Experimental Medicine. 2006; 203: 1903-1913. (Cover and highlighted article).
Chyou S, Ekland EH, Carpenter AC, Tzeng T, Tian S, Michaud M, Madri JA, and Lu TT. Fibroblast-type reticular stromal cells regulate the lymph node vasculature. Journal of Immunology. 2008; 181:3887-3896.
Tzeng T, Chyou S, Tian S, Webster B, Carpenter AC, Guaiquil VH, and Lu TT. CD11chi dendritic cells regulate the reestablishment of vascular quiescence and stabilization after immune stimulation of lymph nodes. Journal of Immunology. 2010; 184:4247-4257.
Lu TT, Kim H, Ma X. Commentary: IL-17, a new kid on the block of tertiary lymphoid organs. Cellular and Molecular Immunology. Epub ahead of print, Sept 19, 2011.
Lu TT. Invited review: Dendritic cells: Novel players in fibrosis and scleroderma. Current Rheumatology Reports. Epub ahead of print, Oct 18, 2011.
Chyou S, Benahmed F, Tian S, Chen J, Kumar V, Lipp M, and Lu TT. Coordinated regulation of lymph node vascular-stromal growth first by CD11c+ cells and then by T and B cells. Journal of Immunology. 2011. 187:5558-67.
Biswas PS, Gupta S, Stirzaker R, Kumar V, Jessberger R, Lu TT, Bhagat G, Pernis AB. Dual regulation of IRF4 function in T and B cells is required for the coordination of T–B cell interactions and the prevention of autoimmunity. Journal of Experimental Medicine. 2012. 209:581-596.
Chyou S, Tian S, Ekland E, and Lu TT. Normalization of the Lymph Node T Cell Stromal Microenvironment in lpr/lpr Mice Is Associated With SU5416-induced Reduction in Autoantibodies, PLoS ONE. 2012. 7:332828.
Benahmed F and Lu TT. Invited Federation of Clinical Immunology Societies (FOCIS) review: Regulating lymph node vascular-stromal growth and function to regulate immunity. Clinical Immunology. 2012. 144:109-116.
Kumar V, Chyou S, Stein JV, and Lu TT. Optical projection tomography reveals dynamics of HEV growth after protein plus CFA immunization and features shared with HEVs in acute autoinflammatory lymphadenopathy. Frontiers in Antigen Presenting Cell Biology. 2012. 3: 282.
Lu TT and Browning JL. Invited review: Role of the Lymphotoxin/LIGHT Axis in the Development and Maintenance of Reticular Networks and Vasculature in Lymphoid Tissues. Frontiers in Immunology. 2014. 5:47.
Benahmed F, Chyou S, Chen J, Dasoveanu D, Kumar, V, Iwakura Y, and Lu TT. Multiple CD11c+ cells collaboratively express IL-1ß to modulate stromal VEGF and lymph node vascular-stromal growth. Journal of Immunology. 2014. 192: 4153-63.
Kumar V, Dasoveanu DC, Chyou S, Tzeng TC, Rozo C, Liang Y, Stohl W, Fu YX, Ruddle NH, and Lu TT. A dendritic cell-stromal axis maintains immune responses in lymph nodes. Immunity. 2015. 43:719-730. (Cover)
For more publications, please see the PubMed listing.
Secondary lymphoid tissues such as lymph nodes are the sites of primary immune responses. These lymphoid tissues grow rapidly and robustly during an immune response, and this growth is accompanied by growth of the blood vessels. Although work in recent years has delineated the regulation of vascular growth in a number of systems, the regulation of lymphoid tissue vessel growth is not well understood. However, because blood vessels of the lymphoid tissues are critical for the delivery of oxygen, micronutrients, and cells, manipulating the growth of blood vessels may be a means to manipulate immune function.
We have identified a role for dendritic or other CD11c+ cells and for fibroblastic reticular cells in regulating lymph node vascular growth. In lymph nodes, blood vessels are suspended in a reticular network composed of collagen-rich fibrils that are ensheathed by fibroblastic reticular cells. We have shown that fibroblastic reticular cells are the main VEGF mRNA-expressing cell type within lymph nodes. Dendritic cells are directly attached to the reticular network and are enriched in vessel-rich areas. Our model is currently that dendritic cells that are activated by the immune stimulus induce fibroblastic reticular cells to upregulate VEGF, which leads to endothelial cell proliferation. Dendritic cells are best known for their function in presenting antigen to T cells; we propose that also play a role in preparing the lymph node vascular-stromal microenvironment for the ensuing immune response.
After vascular expansion, there is a stage of vascular quiescence and stabilization whereby proliferation of the newly expanded vasculature is downregulated and the vessels are made less leaky. We have identified a role for a distinct subset of late-accumulating dendritic cells in regulating vascular quiescence and stabilization and are currently trying to understand how these dendritic cells work. We have also shown that disruption of vascular quiescence and stabilization is associated with disrupted B cell responses. Abnormal B cell responses in autoimmune diseases such as lupus lead to the generation of pathogenic autoantibodies which cause inflammation in skin, kidney and other internal organs. We are testing the possibility that disruption of vascular quiescence and stabilization could be a novel means by which to control pathogenic autoantibody generation.
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As of March 26, 2015, Dr. Lu reported no financial interest relationships with healthcare industry.
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