Imm - Kbase Transcription Profiling Projects

(1) Macrophages in Adenovirus Infected Liver:
Innate immunity plays a significant role in anti-viral responses. Macrophages are a major innate cell type and are considered an important cell type in this response. We have found that macrophages, perhaps in the form of Kupffer cells, upregulated many surface antigens and produce cytokines and chemokines to mediate T cell and NK cell activation and leukocyte infiltration. The Mode/Mechanism of Actin of macrophage activation in the early phase of virus infection is unclear. We have performed a microarray analysis on liver macrophages on the second day after adenovirus infection. The aim is to identify genes and pathways involved in anti-viral responses.

     

Collaborator: Dr. Young S. Hahn

(2) Dendritic Cells in Asthma:
Dendritic cells are present in the lung parenchyma, often juxtaposed against the airway epithelial cells, and may extend their pseudopods into the airway lumen to capture airborne allergens present in lungs. They play a key role in allergen-specific responses by presenting captured allergens to T cells, thereby activating T cells and other cell types downstream of T cell activation. There are 2 major phenotypically and functionally distinct conventional DC subsets in lungs, the CD103+ DC and the CD11b-high DC. CD103+ DC can traverse the airway epithelium by the expression of tight junction proteins. They are the major DC type in delivering airway allergens to the lung-draining lymph nodes. CD103+ DC also preferentially internalized apoptotic cells, present antigens to CD8+ cytotoxic T cells, and cross present viral antigens and tumor cell antigens to CD8+ T cells. They also play a regulatory role by activating regulatory T cells. CD11b-high DC, on the other hand, preferentially present antigens to CD4 + helper T cells, and produce cytokines, chemokines, No, arachidonic acid metabolites, and reactive oxygen species in mediating various immune reactions. An asthma model was established by intratracheally immunizing mice with a surrogate DC in lung-draining lymph nodes of intratracheally immunized mice are activated DC. In this experiment, we have analyzed gene expression profiles of CD103+ DC and CD11b-high DC in naive mouse lung and in lung-draining lymph nodes of intratracheally immunized mice. We hope to identify the differences in the pathways active in CD103+ and CD11b-high lung DC under homeostatic conditions. In addition, we hypothesize that DC are activated as they migrate to the lung-draining lymph node after immunization. The pathways activated by immunization in each of the DC types will be elucidated.

     

Collaborator: Dr. C. Edward Rose, Jr.

(3) Dendritic Cells and Macrophages in Lupus Nephritis and other Glomerulonephritis:

Glomerulonephritis and proteinuria is an important clinical manifestation of Systemic Lupus Erythematosus (SLE Network Map) and often lead to end stage renal disease. Extensive glomerular and tubular damage occurs in patients with severe disease. A spontaneous model of SLE with severe proteinuria is established with the NZM2328 mouse strain. Damages due to DC and macrophage functions are considered to be significant events leading to eventual kidney damage and malfunction. We have isolated kidney CD103+ DC, CD11b-hi DC, and macrophages for microarray analysis. The data will identify differences in cellular function among the DC and macrophage cell types in the pathogenesis of glomerulonephritis. We also have a congenic mouse strain with a genetic difference of only 45 genes in 1.4 Mb DNA. This congenic strain does not exhibit severe proteinuria. Eventual analysis of this mouse strain may lead to the identification of pathway and genes involved in glomerulonephritis and may identify genes expressed by non-hematopoietic cell types in the kidney.

     

Collaborators: Dr. Shu Man Fu and Dr. Sun-sang J. Sung

(4) Mesangial cells and IgA nephropathy:

IgA nephropathy is the most common form of glomerulonephritis, and is particularly common in Asians. A large percentage of the patients eventually develops end stage renal disease requiring kidney transplants. The pathogenesis of the disease is unknown and in transplant patients, relapse of glomerulonephritis symptoms is often unresponsive to treatment. Thus the disease poses a significant public health threat. IgA deposition in the mesangium is an important triggering event in the pathogenesis of IgA nephropathy and the aberrant structure in the carbohydrate moiety of IgA has been postulated to be important for disease development. Because mesangial cells are important in the pathogenesis of IgA nephropathy, we have isolated mesangial cells by cell sorting and used the isolated RNA for microarray analysis. It is postulated that in this mesangial cell array, we can identify genes that encode IgA-binding molecules and pathways involved in the pathogenesis of IgA nephropathy.

Collaborators: Dr. Thu Le and Dr. W. Kline Bolton
First set up on November 22, 2011, last updated on February 02, 2012 by Dr. Jeff Chen.