Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice.

Research output: Contribution to journalArticle

Abstract

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. Furthermore, mice depleted of granulocytes were resistant to disease development. In contrast, certain acute inflammatory mediators (C5, Fcγ receptor III, mast cells, and histamine) and adaptive immune players (αβ T and B cells) were redundant in disease induction. Hence, we propose that mannan-induced activation of macrophages leads to TNF-α secretion and stimulation of local γδ T cells secreting IL-17A. The combined action of activated macrophages and IL-17A produced in situ drives neutrophil infiltration in the epidermis and dermis of the skin, leading to disease manifestations. Thus, our finding suggests a new mechanism triggered by exposure to exogenous microbial components, such as mannan, that can induce and exacerbate Ps and PsA.

Details

Authors
  • Ia Khmaladze
  • Tiina Kelkka
  • Simon Guerard
  • Kajsa Wing
  • Angela Pizzolla
  • Amit Saxena
  • Katarina Lundqvist
  • Meirav Holmdahl
  • Nandakumar Kutty Selva
  • Rikard Holmdahl
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Dermatology and Venereal Diseases
  • Cell and Molecular Biology
  • Immunology in the medical area
Original languageEnglish
Pages (from-to)E3669-E3678
JournalProceedings of the National Academy of Sciences
Volume111
Issue number35
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Dermatology and Venereology (Lund) (013006000), Vessel Wall Biology (013212028), Medical Inflammation Research (013212019)