THE ROLE OF MUCOSAL ANTIGEN-PRESENTING CELLS IN REGULATING IMMUNE RESPONSES

Emory University, Atlanta GA

Investigators

Linked publications, trials & patents

Abstract

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. During the previous year of this project, we continued to make significant progress in addressing the Specific Aims of the original proposal. We are now continuing this work via this competitive renewal of the original proposal, titled 'Microbes, Dendritic Cells Subsets and T-cell Immunity.' We had previously described a population of CD11b+F4/80+CD11c- macrophages in the lamina propria that expressed several anti-inflammatory molecules, including interleukin 10 (IL-10), but little or no proinflammatory cytokines, even after stimulation with Toll-like receptor ligands (Denning et al, Nature Immunology 2007). These macrophages induced, by a mechanism dependent on IL-10, retinoic acid and exogenous transforming growth factor-beta, the differentiation of Foxp3+ regulatory T cells. In contrast, lamina propria CD11b+ dendritic cells elicited IL-17 production. This IL-17 production was suppressed by lamina propria macrophages, indicating that a dynamic interaction between these subsets may influence the balance between immune activation and tolerance. The present grant is following up on these observations.