Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice
Ia Khmaladze, Tiina Kelkka, Simon Guerard, Kajsa Wing, Angela Pizzolla, Amit Saxena, Katarina Lundqvist, Meirav Holmdahl, Kutty Selva Nandakumar, Rikard Holmdahl
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2014
Psoriasis (Ps) and psoriasis arthritis (PsA) are poorly understood common diseases, induced by unknown environmental factors, affecting skin and articular joints. A single i.p. exposure to mannan from Saccharomyces cerevisiae induced an acute inflammation in inbred mouse strains resembling human Ps and PsA-like disease, whereas multiple injections induced a relapsing disease. Exacerbation of disease severity was observed in mice deficient for generation of reactive oxygen species (ROS). Interestingly, restoration of ROS production, specifically in macrophages, ameliorated both skin and joint disease. Neutralization of IL-17A, mainly produced by γδ T cells, completely blocked disease symptoms..View full abstract
Awarded by European Union Masterswitch
We thank Carlos and Kristina Palestro and Tomasz Klaczkowski for taking care of animals. This study was supported by the Swedish Strategic Science Foundation, the Knut and Alice Wallenberg Foundation, the Konung Gustaf V:s 80-ars fond, the Swedish Research Council, the Swedish Rheumatism Association, European Union Masterswitch (Grant HEALTH-F2-2008-223404), Neurinox, and BeTheCure.