Abstract
METHODS: To determine the role of IRF3 in autoimmune inflammation, we immunised wild-type (WT) and irf3-/- mice to induce EAE. Splenocytes from WT and irf3-/- mice were also activated in vitro in Th17-polarising conditions.
RESULTS: Clinical signs of disease were significantly lower in mice lacking IRF3, with reduced Th1 and Th17 cells in the central nervous system. Peripheral T-cell responses were also diminished, including impaired proliferation and Th17 development in irf3-/- mice. Myelin-reactive CD4+ cells lacking IRF3 completely failed to transfer EAE in Th17-polarised models as did WT cells transferred into irf3-/- recipients. Furthermore, IRF3 deficiency in non-CD4+ cells conferred impairment of Th17 development in antigen-activated cultures.
CONCLUSION: These data show that IRF3 plays a crucial role in development of Th17 responses and EAE and warrants investigation in human multiple sclerosis.
| Original language | English |
|---|---|
| Journal | Journal of neuroinflammation |
| Volume | 11 |
| Issue number | 130 |
| DOIs | |
| Publication status | Published - 28 Jul 2014 |
Fingerprint
Keywords
- Multiple Sclerosis
- IRF3
- Th17
- EAE
Cite this
}
Interferon regulatory factor (IRF) 3 is critical for the development of experimental autoimmune encephalomyelitis. / Fitzgerald, Denise; O'Brien, Kate; Young, Andrew; Fonseca-Kelly, Zoe; Rostami, Abdolmohamad; Gran, Bruno.
In: Journal of neuroinflammation, Vol. 11, No. 130, 28.07.2014.Research output: Contribution to journal › Article
TY - JOUR
T1 - Interferon regulatory factor (IRF) 3 is critical for the development of experimental autoimmune encephalomyelitis.
AU - Fitzgerald, Denise
AU - O'Brien, Kate
AU - Young, Andrew
AU - Fonseca-Kelly, Zoe
AU - Rostami, Abdolmohamad
AU - Gran, Bruno
PY - 2014/7/28
Y1 - 2014/7/28
N2 - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune inflammatory demyelination that is mediated by Th1 and Th17 cells. The transcription factor interferon regulatory factor 3 (IRF3) is activated by pathogen recognition receptors and induces interferon-beta production.METHODS: To determine the role of IRF3 in autoimmune inflammation, we immunised wild-type (WT) and irf3-/- mice to induce EAE. Splenocytes from WT and irf3-/- mice were also activated in vitro in Th17-polarising conditions.RESULTS: Clinical signs of disease were significantly lower in mice lacking IRF3, with reduced Th1 and Th17 cells in the central nervous system. Peripheral T-cell responses were also diminished, including impaired proliferation and Th17 development in irf3-/- mice. Myelin-reactive CD4+ cells lacking IRF3 completely failed to transfer EAE in Th17-polarised models as did WT cells transferred into irf3-/- recipients. Furthermore, IRF3 deficiency in non-CD4+ cells conferred impairment of Th17 development in antigen-activated cultures.CONCLUSION: These data show that IRF3 plays a crucial role in development of Th17 responses and EAE and warrants investigation in human multiple sclerosis.
AB - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune inflammatory demyelination that is mediated by Th1 and Th17 cells. The transcription factor interferon regulatory factor 3 (IRF3) is activated by pathogen recognition receptors and induces interferon-beta production.METHODS: To determine the role of IRF3 in autoimmune inflammation, we immunised wild-type (WT) and irf3-/- mice to induce EAE. Splenocytes from WT and irf3-/- mice were also activated in vitro in Th17-polarising conditions.RESULTS: Clinical signs of disease were significantly lower in mice lacking IRF3, with reduced Th1 and Th17 cells in the central nervous system. Peripheral T-cell responses were also diminished, including impaired proliferation and Th17 development in irf3-/- mice. Myelin-reactive CD4+ cells lacking IRF3 completely failed to transfer EAE in Th17-polarised models as did WT cells transferred into irf3-/- recipients. Furthermore, IRF3 deficiency in non-CD4+ cells conferred impairment of Th17 development in antigen-activated cultures.CONCLUSION: These data show that IRF3 plays a crucial role in development of Th17 responses and EAE and warrants investigation in human multiple sclerosis.
KW - Multiple Sclerosis
KW - IRF3
KW - Th17
KW - EAE
U2 - 10.1186/1742-2094-11-130
DO - 10.1186/1742-2094-11-130
M3 - Article
VL - 11
JO - Journal of neuroinflammation
JF - Journal of neuroinflammation
SN - 1742-2094
IS - 130
ER -