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

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Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice. / Khmaladze, Ia; Kelkka, Tiina; Guerard, Simon; Wing, Kajsa; Pizzolla, Angela; Saxena, Amit; Lundqvist, Katarina; Holmdahl, Meirav; Kutty Selva, Nandakumar; Holmdahl, Rikard.

I: Proceedings of the National Academy of Sciences, Vol. 111, Nr. 35, 2014, s. E3669-E3678.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Khmaladze, I, Kelkka, T, Guerard, S, Wing, K, Pizzolla, A, Saxena, A, Lundqvist, K, Holmdahl, M, Kutty Selva, N & Holmdahl, R 2014, 'Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice.', Proceedings of the National Academy of Sciences, vol. 111, nr. 35, s. E3669-E3678. https://doi.org/10.1073/pnas.1405798111

APA

Khmaladze, I., Kelkka, T., Guerard, S., Wing, K., Pizzolla, A., Saxena, A., ... Holmdahl, R. (2014). Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice. Proceedings of the National Academy of Sciences, 111(35), E3669-E3678. https://doi.org/10.1073/pnas.1405798111

CBE

Khmaladze I, Kelkka T, Guerard S, Wing K, Pizzolla A, Saxena A, Lundqvist K, Holmdahl M, Kutty Selva N, Holmdahl R. 2014. Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice. Proceedings of the National Academy of Sciences. 111(35):E3669-E3678. https://doi.org/10.1073/pnas.1405798111

MLA

Vancouver

Author

Khmaladze, Ia ; Kelkka, Tiina ; Guerard, Simon ; Wing, Kajsa ; Pizzolla, Angela ; Saxena, Amit ; Lundqvist, Katarina ; Holmdahl, Meirav ; Kutty Selva, Nandakumar ; Holmdahl, Rikard. / Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice. I: Proceedings of the National Academy of Sciences. 2014 ; Vol. 111, Nr. 35. s. E3669-E3678.

RIS

TY - JOUR

T1 - Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice.

AU - Khmaladze, Ia

AU - Kelkka, Tiina

AU - Guerard, Simon

AU - Wing, Kajsa

AU - Pizzolla, Angela

AU - Saxena, Amit

AU - Lundqvist, Katarina

AU - Holmdahl, Meirav

AU - Kutty Selva, Nandakumar

AU - Holmdahl, Rikard

N1 - 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)

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.1405798111

DO - 10.1073/pnas.1405798111

M3 - Article

VL - 111

SP - E3669-E3678

JO - Proceedings of the National Academy of Sciences

T2 - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 35

ER -