Publication

Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes

Wiersma, V. R., Clarke, A., Pouwels, S. D., Perry, E., Abdullah, T. M., Kelly, C., Soyza, A. D., Hutchinson, D., Eggleton, P. & Bremer, E., 19-Aug-2019, In : International Journal of Molecular Sciences. 20, 16, 20 p., 4046.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Wiersma, V. R., Clarke, A., Pouwels, S. D., Perry, E., Abdullah, T. M., Kelly, C., Soyza, A. D., Hutchinson, D., Eggleton, P., & Bremer, E. (2019). Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes. International Journal of Molecular Sciences, 20(16), [4046]. https://doi.org/10.3390/ijms20164046

Author

Wiersma, Valerie R ; Clarke, Alex ; Pouwels, Simon D ; Perry, Elizabeth ; Abdullah, Trefa M ; Kelly, Clive ; Soyza, Anthony De ; Hutchinson, David ; Eggleton, Paul ; Bremer, Edwin. / Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes. In: International Journal of Molecular Sciences. 2019 ; Vol. 20, No. 16.

Harvard

Wiersma, VR, Clarke, A, Pouwels, SD, Perry, E, Abdullah, TM, Kelly, C, Soyza, AD, Hutchinson, D, Eggleton, P & Bremer, E 2019, 'Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes', International Journal of Molecular Sciences, vol. 20, no. 16, 4046. https://doi.org/10.3390/ijms20164046

Standard

Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes. / Wiersma, Valerie R; Clarke, Alex; Pouwels, Simon D; Perry, Elizabeth; Abdullah, Trefa M; Kelly, Clive; Soyza, Anthony De; Hutchinson, David; Eggleton, Paul; Bremer, Edwin.

In: International Journal of Molecular Sciences, Vol. 20, No. 16, 4046, 19.08.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Wiersma VR, Clarke A, Pouwels SD, Perry E, Abdullah TM, Kelly C et al. Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes. International Journal of Molecular Sciences. 2019 Aug 19;20(16). 4046. https://doi.org/10.3390/ijms20164046


BibTeX

@article{57a8e8ba79ed43ac8bce59cf84e0fbbc,
title = "Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes",
abstract = "The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.",
author = "Wiersma, {Valerie R} and Alex Clarke and Pouwels, {Simon D} and Elizabeth Perry and Abdullah, {Trefa M} and Clive Kelly and Soyza, {Anthony De} and David Hutchinson and Paul Eggleton and Edwin Bremer",
year = "2019",
month = aug,
day = "19",
doi = "10.3390/ijms20164046",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1422-0067",
publisher = "MDPI AG",
number = "16",

}

RIS

TY - JOUR

T1 - Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes

AU - Wiersma, Valerie R

AU - Clarke, Alex

AU - Pouwels, Simon D

AU - Perry, Elizabeth

AU - Abdullah, Trefa M

AU - Kelly, Clive

AU - Soyza, Anthony De

AU - Hutchinson, David

AU - Eggleton, Paul

AU - Bremer, Edwin

PY - 2019/8/19

Y1 - 2019/8/19

N2 - The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.

AB - The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.

U2 - 10.3390/ijms20164046

DO - 10.3390/ijms20164046

M3 - Article

C2 - 31430907

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 16

M1 - 4046

ER -

ID: 94578990