This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The discovery of a new lineage of helper T cells that selectively produces interleukin (IL)-17 has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. For various lung diseases, elevated Th17 cells and their secretory products, IL-17A, IL-17F are also noticed. However, the nature of the presence and the function related to IL-17 and Th17 cells remain unclear. For non-human primate, there is a lack of information on the functional roles of Th17 cells and their secretory products in various diseases and inflammatory conditions. Since non-human primate monkey is the closest animal to human, the development of Th17 cell lineage in vitro must be carried out in order to apply the new knowledge into various diseases. For Respiratory Disease Unit at CNRPC, there is an unique opportunity to utilize the adoptive transfer approach to characterize the functions of Th17 cells and their secretory products in the ongoing lung injury and asthma model, supported by NIEHS for past 30 years. The current hypothesis in the pilot project application is that the plasticity of Th17 cell lineage and function is regulated by various cytokines and mediators present in the mucosal immunity. To test this hypothesis, we will develop an in vitro system for non-human primate Th17 cell differentiation from the progenitor cells present in umbilical cord blood and to study the responses of this cell lineage to various cytokines and mediators. We believe this is the first of such a study for non-human primate Th17 cell lineage.
Two specific aims are proposed.
Aim 1 is to establish an in vitro culture system where non-human primate T na?ve cells can differentiate into Th17 cell lineage.
The second aim i s to examine the plasticity of Th17 cell differentiation in response to various cytokines in vitro. Information obtained from these studies will serve as the basis of adoptive transfer experiments to exam the role of Th17 cells in lung diseases.
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