Exploring Epithelial-Immune Interactions Using Organoid-based
Systems:
Reconstructing thymic and intestinal models in
vitro
Sangho Lim, Ph.D.
Graduate School of
Stem Cell and Regenerative Medicine
Korea Advanced Institute of Science and Technology (KAIST)
Organoid-immune cell co-culture systems provide a
versatile platform to reconstruct human epithelial-immune interactions in
vitro, offering new opportunities to study how immune cells communicate
with epithelial (stem) cells. Building on this concept, we established an adult
tissue-derived thymic epithelial cell (TEC) organoid system that faithfully
recapitulates TEC differentiation and immune education processes in the thymus.
RANKL-dependent maturation of TECs generated functionally competent epithelial
cells capable of supporting early T cell development, effectively modeling the
epithelial-immune crosstalk within the thymic microenvironment.
Extending this approach, we utilized human intestinal stem cell-derived
organoids to elucidate the differentiation and function of microfold (M) cells.
We proposed a human M cell differentiation trajectory and demonstrated that
human M cells exhibit both transcriptional and functional resemblance to
dendritic cells, highlighting their unexpected roles as epithelial
antigen-presenting cells. RANKL-dependent M cell maturation induced
constitutive MHC class II expression and antigen processing, enabling direct antigen
presentation to CD4+ T cells and unveiling a previously unrecognized
mechanism of mucosal immune activation.
Together, these organoid-based co-culture systems enable controlled
reconstruction of epithelial-immune interfaces across distinct tissues. They
provide a human-relevant and experimentally tractable platform to investigate
epithelial (stem) cell-immune interactions, tissue regeneration, and
immune-mediated diseases, bridging fundamental immunology with epithelial and stem
cell biology.
