This project aims to elucidate roles and functional features of long noncoding RNAs (lncRNAs) in establishing and maintaining immune responses by studying infected dendritic cells type-1 (DC1).

Dendritic cells (DCs) are antigen-presenting cells which function as the control center of immune responses. When infected with Toxoplasma gondii, or other intracellular pathogens, dendritic cells type-1 (DC1) turn on the host defense programs that allow them to prime adaptive immune T-cells to fight the infection. It has been previously shown that expression profiles of mRNAs responsible for activation of infected DC1s are established early on during differentiation through extensive chromatin remodeling and activation Kurotaki et al, PNAS, 119 (34) e2207009119, 2022 . However, many details of how functional landscape of DC1 is established and regulated remain unknown.

Concurrent recent reports have suggested involvement of long noncoding RNAs (lncRNAs) in the regulation of the pathogenic infections; reviewed in Front Cell Infect Microbiol., 13, 1160198, 2023 . Nonetheless, it remains unknown how majority lncRNAs regulate responses to infection.

While investigating roles of lncRNAs in regulating DC type1 (DC1) differentiation, we also sought to understand how lncRNAs can establish and maintain DC1 responses to infection. Our preliminary analyses uncovered hundreds of differentially expressed known and novel lncRNAs in DC1s infected with Toxoplasma gondii.

Fig: Chromatin structure re-arrangement and activation at gene loci related to host defense occur progressively during various stages of DC1 development (Kurotaki et. al., 2022)