Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice.
(2014) In Proceedings of the National Academy of Sciences 111(35). p.3669-3678- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4614380
- author
- Khmaladze, Ia ; Kelkka, Tiina ; Guerard, Simon ; Wing, Kajsa ; Pizzolla, Angela LU ; Saxena, Amit LU ; Lundqvist, Katarina LU ; Holmdahl, Meirav LU ; Kutty Selva, Nandakumar LU and Holmdahl, Rikard LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 111
- issue
- 35
- pages
- 3669 - 3678
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:25136095
- wos:000341230800014
- scopus:84907228016
- pmid:25136095
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1405798111
- language
- English
- LU publication?
- yes
- additional info
- 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)
- id
- 4f3afd7c-e904-40b9-8b80-b69d85b83949 (old id 4614380)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25136095?dopt=Abstract
- date added to LUP
- 2016-04-01 11:15:08
- date last changed
- 2022-04-20 18:07:43
@article{4f3afd7c-e904-40b9-8b80-b69d85b83949,
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.}},
author = {{Khmaladze, Ia and Kelkka, Tiina and Guerard, Simon and Wing, Kajsa and Pizzolla, Angela and Saxena, Amit and Lundqvist, Katarina and Holmdahl, Meirav and Kutty Selva, Nandakumar and Holmdahl, Rikard}},
issn = {{1091-6490}},
language = {{eng}},
number = {{35}},
pages = {{3669--3678}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice.}},
url = {{http://dx.doi.org/10.1073/pnas.1405798111}},
doi = {{10.1073/pnas.1405798111}},
volume = {{111}},
year = {{2014}},
}