Therapeutics/pharmacology

Oral

Dedifferentiation of Human Terminally Differentiated Dendritic Cells Shuts down Their Innate and Adaptive Immune Mechanisms

Wednesday, June 14
6:15 PM - 7:45 PM

Induced pluripotent stem cells (iPSC) can be used to generate donor-specific desired cell types, including naive immune effectors. Although donor-derived iPSC lines are believed to be genetically and immunologically matched, studies in mouse models have claimed that the syngenic mouse iPSC lines can be immunogenic. Therefore, a greater understanding of the inherent immunogenicity of human iPSC and their cellular derivatives is needed for the development of safe and effective cell replacement therapies (CRT). We here report characterization of the innate and adaptive-immune mechanisms in human DC-derived iPSC lines. We show that these iPSC lines express mRNAs of Toll Like Receptor (TLR) molecules and the antigen-presentation pathway intermediates, however, these mRNAs are not translated into functional proteins, and these iPSC lines do not induce TLR-mediated inflammatory cytokine response or inflammasome activation. We also show that these iPSC lines do not activate T cells in an allogenic mixed lymphocyte reaction (MLR), however, they do express low-levels of MHC class I molecules that can efficiently acquire antigenic peptides from their microenvironment and present them to antigen-specific T cells. In addition, we show that these iPSC lines can be efficiently differentiated into hematopoietic stem cell (HSC) precursors as well as antigen presenting cells. Taken together, our data show that de-differentiation of human DC effectively shuts down their immunogenic pathways and implicate transcriptional as well as post-transcriptional mechanisms in this process. Our findings demonstrate that human DC-derived iPSC lines could be useful to understand the development of innate and adaptive immune mechanisms in human DC.

Arvind Chhabra

Assistant Professor in Residence
University of Connecticut Health Center

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    Deepika Batra

    Research Assistant
    University of Connecticut Health Center

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