Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine
Yong Chen, Zilong Wang, Michele Yeo, Qiaojuan Zhang, Ana E. López-Romero, Huiping Ding, Xin Zhang, Qian Zeng, Sara L. Morales‐Lázaro, Carlene Moore, Yingai J. Jin, Huanghe Yang, Johannes Morstein, Andrey V. Bortsov, Marcin Krawczyk, Frank Lammert, Manal F. Abdelmalek, Anna Mae Diehl, Piotr Milkiewicz, Andreas E. Kremer, Jennifer Zhang, Andrea G. Nackley, Tony E. Reeves, Mei‐Chuan Ko, Ru‐Rong Ji, Tamara Rosenbaum, Wolfgang Liedtke
Abstract
BACKGROUND & AIMS: Limited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus. METHODS: imaging assays. Sera from patients with primary biliary cholangitis were used for measuring the levels of LPC and miR-146a. RESULTS: sensory neurons to cause itch. LPC and miR-146a levels were both elevated in sera of patients with primary biliary cholangitis with itch and correlated with itch intensity. Moreover, LPC and miR-146a were also increased in sera of cholestatic mice and elicited itch in nonhuman primates. CONCLUSIONS: pruriceptor sensory neurons. Our findings support the new concept of the skin, as a sensory organ, playing a critical role in cholestatic itch, beyond liver, peripheral sensory neurons, and central neural pathways supporting pruriception.