2005 General Immune System Function
2011 General Immune System Function, Skin
In lupus, the immune system goes awry.
With her 2005 Novel Research Grant, Dr. Lu explored the mechanisms at play in jump-starting and fueling this faulty autoimmune response. A pediatric rheumatologist, she proposed viewing Type 1 interferons in a novel way: as pro-inflammatory compounds that lead to the growth of lymph node blood vessels. Could this development set the stage for the inappropriate immune system responses characteristic of lupus, she wondered?
The approach represented a whole new way of thinking.
Ultimately, Dr. Lu reported finding that dendritic cells can indeed stimulate blood vessel growth, but that type-1 interferon is not required. She is currently looking for the essential factor involved. In parallel, Dr. Lu reported in 2010 that the LRI grant also enabled her and colleagues to establish that a subset of dendritic cells initiate lymphoid tissue vascular expansion.
With her 2011 Novel Research Grant, Dr. Lu will examine a different aspect of lupus.
Many people with lupus suffer from inflammatory skin lesions after being exposed to the sun. The reason for this reaction, known as “photosensitivity,” remains something of a mystery.
Dr. Lu is tackling this problem with a novel idea that zeroes in on the initial blood vessel activation that permits inflammatory cells from the bloodstream to enter the skin. She hypothesizes that this process is heightened in people with lupus because of an imbalance between mature and immature forms of immune system “guard” or “sentinel” cells called “Langerhans Cells.”
If the scales are indeed tipped towards a greater volume of mature LC cells in lupus, it’s understandable that there is an excess activation of blood vessels in the skin and related inflammation—and that exposure to ultraviolet light from the sun only worsens the situation.
Discoveries from this study could lead to exciting new approaches to preventing or treating the often devastating photosensitivity and skin manifestations of lupus that affect the quality of life for so many.
Select publications from 2005 Grant:
Regulation of lymph node vascular growth by dendritic cells. Webster B, Ekland EH, Agle LM, Chyou S, Ruggieri R, Lu TT. J Exp Med. 2006 Aug 7;203(8):1903-13.
CD11chi dendritic cells regulate the re-establishment of vascular quiescence and stabilization after immune stimulation of lymph nodes. Tzeng TC, Chyou S, Tian S, Webster B, Carpenter AC, Guaiquil VH, Lu TT. J Immunol. 2010 Apr 15;184(8):4247-57.
Ongoing funding from 2005 Grant:
Dr. Lu won an NIH grant for $1.125 million to further expand on her LRI findings, as well as a $1.5 million R01 grant to explore targeting the vasculature as a means of reducing the autoimmune response.
Rev. March 2011