Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade. / Atkinson, Sara Marie; Hoffmann, Ute; Bach, Emil; Danneskiold-Samsøe, Niels Banhos; Kristiansen, Karsten; Serikawa, Kyle ; Fox, Brian ; Kruse, Kim; Haase, Claus; Skov, Søren; Nansen, Anneline.

I: Disease Models & Mechanisms, Bind 9, 2016, s. 427-440.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Atkinson, SM, Hoffmann, U, Bach, E, Danneskiold-Samsøe, NB, Kristiansen, K, Serikawa, K, Fox, B, Kruse, K, Haase, C, Skov, S & Nansen, A 2016, 'Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade', Disease Models & Mechanisms, bind 9, s. 427-440. https://doi.org/10.1242/dmm.022905

APA

Atkinson, S. M., Hoffmann, U., Bach, E., Danneskiold-Samsøe, N. B., Kristiansen, K., Serikawa, K., Fox, B., Kruse, K., Haase, C., Skov, S., & Nansen, A. (2016). Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade. Disease Models & Mechanisms, 9, 427-440. https://doi.org/10.1242/dmm.022905

Vancouver

Atkinson SM, Hoffmann U, Bach E, Danneskiold-Samsøe NB, Kristiansen K, Serikawa K o.a. Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade. Disease Models & Mechanisms. 2016;9:427-440. https://doi.org/10.1242/dmm.022905

Author

Atkinson, Sara Marie ; Hoffmann, Ute ; Bach, Emil ; Danneskiold-Samsøe, Niels Banhos ; Kristiansen, Karsten ; Serikawa, Kyle ; Fox, Brian ; Kruse, Kim ; Haase, Claus ; Skov, Søren ; Nansen, Anneline. / Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade. I: Disease Models & Mechanisms. 2016 ; Bind 9. s. 427-440.

Bibtex

@article{d8306e7f087d4e02b6545834d152af35,
title = "Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade",
abstract = "Rodent models of arthritis have been extensively used in the elucidation of rheumatoid arthritis (RA) pathogenesis and are instrumental in the development of therapeutic strategies. Here we utilise delayed-type hypersensitivity arthritis (DTHA), a model in C57BL/6 mice affecting one paw with synchronised onset, 100% penetrance and low variation. We investigate the role of regulatory T cells (Tregs) in DTHA through selective depletion of Tregs and the role of IL-17 in connection with Treg depletion. Given the relevance of Tregs in RA, and the possibility of developing Treg-directed therapies, this approach could be relevant for advancing the understanding of Tregs in inflammatory arthritis. Selective depletion of Tregs was achieved using a Foxp3-DTR-eGFP mouse, which expresses the diphtheria toxin receptor (DTR) and enhanced green fluorescent protein (eGFP) under control of the Foxp3 gene. Anti-IL-17 monoclonal antibody (mAb) was used for IL-17 blockade. Numbers and activation of Tregs increased in the paw and its draining lymph node in DTHA, and depletion of Tregs resulted in exacerbation of disease as shown by increased paw swelling, increased infiltration of inflammatory cells, increased bone remodelling and increased production of inflammatory mediators, as well as increased production of anti-citrullinated protein antibodies. Anti-IL-17 mAb treatment demonstrated that IL-17 is important for disease severity in both the presence and absence of Tregs, and that IL-17 blockade is able to rescue mice from the exacerbated disease caused by Treg depletion and caused a reduction in RANKL, IL-6 and the number of neutrophils. We show that Tregs are important for the containment of inflammation and bone remodelling in DTHA. To our knowledge, this is the first study using the Foxp3-DTR-eGFP mouse on a C57BL/6 background for Treg depletion in an arthritis model, and we here demonstrate the usefulness of the approach to study the role of Tregs and IL-17 in arthritis.",
author = "Atkinson, {Sara Marie} and Ute Hoffmann and Emil Bach and Danneskiold-Sams{\o}e, {Niels Banhos} and Karsten Kristiansen and Kyle Serikawa and Brian Fox and Kim Kruse and Claus Haase and S{\o}ren Skov and Anneline Nansen",
year = "2016",
doi = "10.1242/dmm.022905",
language = "English",
volume = "9",
pages = "427--440",
journal = "Disease Models & Mechanisms",
issn = "1754-8403",
publisher = "company of biologists",

}

RIS

TY - JOUR

T1 - Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade

AU - Atkinson, Sara Marie

AU - Hoffmann, Ute

AU - Bach, Emil

AU - Danneskiold-Samsøe, Niels Banhos

AU - Kristiansen, Karsten

AU - Serikawa, Kyle

AU - Fox, Brian

AU - Kruse, Kim

AU - Haase, Claus

AU - Skov, Søren

AU - Nansen, Anneline

PY - 2016

Y1 - 2016

N2 - Rodent models of arthritis have been extensively used in the elucidation of rheumatoid arthritis (RA) pathogenesis and are instrumental in the development of therapeutic strategies. Here we utilise delayed-type hypersensitivity arthritis (DTHA), a model in C57BL/6 mice affecting one paw with synchronised onset, 100% penetrance and low variation. We investigate the role of regulatory T cells (Tregs) in DTHA through selective depletion of Tregs and the role of IL-17 in connection with Treg depletion. Given the relevance of Tregs in RA, and the possibility of developing Treg-directed therapies, this approach could be relevant for advancing the understanding of Tregs in inflammatory arthritis. Selective depletion of Tregs was achieved using a Foxp3-DTR-eGFP mouse, which expresses the diphtheria toxin receptor (DTR) and enhanced green fluorescent protein (eGFP) under control of the Foxp3 gene. Anti-IL-17 monoclonal antibody (mAb) was used for IL-17 blockade. Numbers and activation of Tregs increased in the paw and its draining lymph node in DTHA, and depletion of Tregs resulted in exacerbation of disease as shown by increased paw swelling, increased infiltration of inflammatory cells, increased bone remodelling and increased production of inflammatory mediators, as well as increased production of anti-citrullinated protein antibodies. Anti-IL-17 mAb treatment demonstrated that IL-17 is important for disease severity in both the presence and absence of Tregs, and that IL-17 blockade is able to rescue mice from the exacerbated disease caused by Treg depletion and caused a reduction in RANKL, IL-6 and the number of neutrophils. We show that Tregs are important for the containment of inflammation and bone remodelling in DTHA. To our knowledge, this is the first study using the Foxp3-DTR-eGFP mouse on a C57BL/6 background for Treg depletion in an arthritis model, and we here demonstrate the usefulness of the approach to study the role of Tregs and IL-17 in arthritis.

AB - Rodent models of arthritis have been extensively used in the elucidation of rheumatoid arthritis (RA) pathogenesis and are instrumental in the development of therapeutic strategies. Here we utilise delayed-type hypersensitivity arthritis (DTHA), a model in C57BL/6 mice affecting one paw with synchronised onset, 100% penetrance and low variation. We investigate the role of regulatory T cells (Tregs) in DTHA through selective depletion of Tregs and the role of IL-17 in connection with Treg depletion. Given the relevance of Tregs in RA, and the possibility of developing Treg-directed therapies, this approach could be relevant for advancing the understanding of Tregs in inflammatory arthritis. Selective depletion of Tregs was achieved using a Foxp3-DTR-eGFP mouse, which expresses the diphtheria toxin receptor (DTR) and enhanced green fluorescent protein (eGFP) under control of the Foxp3 gene. Anti-IL-17 monoclonal antibody (mAb) was used for IL-17 blockade. Numbers and activation of Tregs increased in the paw and its draining lymph node in DTHA, and depletion of Tregs resulted in exacerbation of disease as shown by increased paw swelling, increased infiltration of inflammatory cells, increased bone remodelling and increased production of inflammatory mediators, as well as increased production of anti-citrullinated protein antibodies. Anti-IL-17 mAb treatment demonstrated that IL-17 is important for disease severity in both the presence and absence of Tregs, and that IL-17 blockade is able to rescue mice from the exacerbated disease caused by Treg depletion and caused a reduction in RANKL, IL-6 and the number of neutrophils. We show that Tregs are important for the containment of inflammation and bone remodelling in DTHA. To our knowledge, this is the first study using the Foxp3-DTR-eGFP mouse on a C57BL/6 background for Treg depletion in an arthritis model, and we here demonstrate the usefulness of the approach to study the role of Tregs and IL-17 in arthritis.

U2 - 10.1242/dmm.022905

DO - 10.1242/dmm.022905

M3 - Journal article

C2 - 26822477

VL - 9

SP - 427

EP - 440

JO - Disease Models & Mechanisms

JF - Disease Models & Mechanisms

SN - 1754-8403

ER -

ID: 165695252