Plasmacytoid dendritic cells (pDCs) represent a unique immune cell lineage that plays an essential role in innate immune responses against viruses. pDCs recognize virus-associated nucleic acids and respond by rapidly secreting massive amounts of type I interferons (IFN), hence their other name: type I interferon- producing cells (IPCs). pDCs can also differentiate, upon activation, into conventional dendritic cells that are capable of presenting antigens to the adaptive arm of the immune system. Thus, pDC are critical for the body's control of viral infections. On the other hand, abnormal pDC hyperactivity has been associated with increased type I IFN levels in autoimmune diseases such as psoriasis and systemic lupus erythematosus. Therefore, pDCs do play important roles in both normal and aberrant immune responses and represent potential useful targets in the treatment of some diseases. pDCs possess unique cellular and molecular characteristics and gene expression profiles that enable them to directly recognize viruses, secrete massive amounts of type I IFN, and differentiate into conventional dendritic cells. Over the last few years, these molecular and cellular features of pDCs have been well characterized; however, the genetic basis of pDC lineage commitment, maturation, and function still remains poorly understood. The overall objective of our research project is to study the role of basic helix-loop-helix transcription factors in the development and function pDCs, and elucidate the pathways that these transcription factors control in pDCs.

Public Health Relevance

These studies will give us insights into the genetic network which controls the development and function of pDC, and may pave the way for the development of new approaches in the treatment of viral infections and some autoimmune disease. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31AI080184-01
Application #
7546392
Study Section
Special Emphasis Panel (ZRG1-IMM-L (29))
Program Officer
Adger-Johnson, Diane S
Project Start
2008-07-01
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
1
Fiscal Year
2008
Total Cost
$45,972
Indirect Cost
Name
Columbia University (N.Y.)
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Ghosh, Hiyaa S; Cisse, Babacar; Bunin, Anna et al. (2010) Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33:905-16
Cisse, Babacar; Caton, Michele L; Lehner, Manfred et al. (2008) Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135:37-48