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Dendritic cells are professional antigen presenting cells playing an important role in initiating antigen-specific immune responses. Being localized in peripheral body sites, dendritic cells continuously endocytose extracellular antigens to monitor the challenge of any foreign agents. Upon contact with inflammatory foreign agents, dendritic cells undergo dramatic biochemical and functional changes called maturation. Maturing dendritic cells halt endocytosis but increase their antigen presentation capacity by upregulating the surface expression of antigen-presenting molecules (called major histocompatibility complexes I/II (MHC I/II)). Maturing dendritic cells migrate to draining lymph nodes to present the peptide antigen/MHC complexes to specific T cells. Recently, Dr. Shin and her colleagues have found that MHCII expression on dendritic cells was controlled by the regulated attachment of small protein called ubiquitin. Her laboratory will further investigate the molecular mechanism of MHCII ubiquitination and how it is controlled during maturation of dendritic cells. Functional roles of the ubiquitination in MHCII will be also addressed in vivo by generating a mutant MHCII knock-in mouse where ubiquitination cannot be performed.

Dr. Shin’s laboratory is also interested in studying the responses of dendritic cells to IgE -bound allergens. Many asthma patients have high level of IgE antibodies against specific allergens to which patients are sensitive. Most of the IgE antibodies in the body are fixed on specific cell types that express high-affinity IgE receptors called Fc eRI. While its expression is limited to mast cells and basophils in rodents, Fc eRI is also expressed on antigen- presenting cells including dendritic cells in humans. Unlike mast cells, however, the cellular responses to Fc eRI/IgE-bound antigen in dendritic cells and its role in the pathogenesis of asthma have been poorly investigated, in part due to the lack of an appropriate animal model. Her laboratory will employ human dendritic cells to study dendritic cell responses to IgE-bound allergens in vitro. These studies will be further extended by developing a mouse model in which Fc eRI is expressed in dendritic cells in vivo to explore the pathophysiological role of IgE-mediated dendritic cell activation in asthma.