This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. T-cell dependent immunity against antigens is heterogeneous with respect to cytokines made by the CD4+ T helper cells (Th cells), and the isotypes of antibodies secreted by the B cells. The type of Th response is critical in determining the clinical outcome of various disease processes. Thus a number of diseases result from a skewing of Th1 to Th2 responses (HIV, allergy), or Th2 to Th1 responses (organ-specific autoimmunity). A deep understanding of Th responses, and the ability to redirect such responses in vivo, may provide attractive strategies for immunotherapy against such diseases. While it is known that the cytokines produced early in a response are crucial in determining the Th polarization of the response, the cell types that initiate the Th polarization in vivo are unknown. The present project seeks to understand roles played by dendritic cells (DCs) in this process. In mice DCs can be calssified into the lymphoid and myeloid families. This research provided a deeper understanding of DCs in the control of Th responses in vivo and will ultimately permit more effective use of DCs for the immunotherapy of autoimmunity and infectious diseases. Work in the past year has focused on defining the subsets of antigen presenting cells, and the nature of the innate immune receptors that regulate the class of the immune responses against pathogens. Highlights include: + The demonstration that distinct subsets of antigen presenting cells differentially regulate T regulatory and Th17 cells. + The demonstration that distinct innate immune receptors on dendritic cells differentially regulate the balance of T regulatory versus Th17 responses. + The demonstration a novel mechanism by which viruses induce type I interferons in plasmacytoid dendritic cells. + The demonstration that systems biology tools can be used to predict the immunity induced by vaccines such as the yellow fever vaccine.
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