Divya Jha, Zainab Al-Taie, Azra Krek, Shadi Toghi Eshghi, Aurelie Fantou, Thomas Laurent, Michael Tankelevich, Xuan Cao, Hadar Meringer, Alexandra E Livanos, Minami Tokuyama, Francesca Cossarini, Arnaud Bourreille, Regis Josien, Ruixue Hou, Pablo Canales-Herrerias, Ryan C Ungaro, Maia Kayal, James Marion, Alexandros D Polydorides, Huaibin M Ko, Darwin D'souza, Raphael Merand, Seunghee Kim-Schulze, Jason A Hackney, Allen Nguyen, Jacqueline M McBride, Guo-Cheng Yuan, Jean Frederic Colombel, Jerome C Martin, Carmen Argmann, Mayte Suárez-Fariñas, Francesca Petralia, Saurabh Mehandru
Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epithelial and immune cell perturbations in active UC. Prominently, reduced frequencies of mature BEST4 + OTOP2 + absorptive and BEST2 + WFDC2 + secretory epithelial enterocytes were associated with the replacement of homeostatic, resident TRDC + KLRD1 + HOPX + γδ + T cells with RORA + CCL20 + S100A4 + T H17 cells and the influx of inflammatory myeloid cells...
June 5, 2023: bioRxiv