Interferon-a: a key factor in autoimmune disease?

Jarka Plskova, Kathrin Greiner, Elizabeth Muckersie, Linda Duncan, John Vincent Forrester

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

PURPOSE. Interferon (IFN)-alpha is an effective drug for treatment of uveitis in Behcet's disease. This study was undertaken to investigate the mechanism of action of IFN-alpha in the treatment of various types of noninfectious sight-threatening uveitis.

METHODS. Eleven patients with refractory uveitis, and 13 healthy individuals were enrolled. The number of circulating plasmacytoid dendritic cells (pDCs) and their capacity to produce IFN-alpha in culture on stimulation with synthetic oligodinucleotides containing the CpG-motif were studied. Peripheral blood CD4(+) T-cell phenotype and activation status were evaluated by flow cytometry at 0, 2, and 8 weeks after treatment for expression of CD69, CD62L, chemokine receptors (CCR4, CXCR3, and CCR5), and intracellular cytokines (TNF-alpha, IFN-gamma, and IL-10).

RESULTS. All patients experienced a positive clinical response to IFN-alpha treatment. There was no significant difference between patients and control subjects in the number of circulating pDCs, but there was a significant decrease in the capability of patients' pDCs to produce IFN-alpha in response to CpG (P < 0.001). Peripheral blood CD4(+) T cells expressed reduced levels of surface CD62L (P < 0.005) as a measure of activation and higher levels of chemokine receptors CXCR3, CCR4, and CCR5 (P < 0.005, P < 0.05, and P < 0.05, respectively); in addition, intracellular T-cell IL-10 levels were increased once the treatment was initiated (P < 0.01).

CONCLUSIONS. The data suggest that IFN-alpha may control uveitis by promoting induction of IL-10-producing T-cells, possibly T-regulatory cells. Dysregulation of the T-cell population in patients with uveitis may be associated with a defect in the pDCs' ability to produce IFN-alpha, which can be circumvented with administration of exogenous IFN-alpha.

Original languageEnglish
Pages (from-to)3946-3950
Number of pages4
JournalInvestigative Ophthalmology & Visual Science
Volume47
Issue number9
DOIs
Publication statusPublished - Sep 2006

Keywords

  • PLASMACYTOID DENDRITIC CELLS
  • CD4(+) T-CELLS
  • IFN-ALPHA
  • TNF-ALPHA
  • ANTIRETROVIRAL THERAPY
  • PERIPHERAL-BLOOD
  • I INTERFERON
  • ACTIVATION
  • INDUCTION
  • UVEITIS

Cite this

Plskova, J., Greiner, K., Muckersie, E., Duncan, L., & Forrester, J. V. (2006). Interferon-a: a key factor in autoimmune disease? Investigative Ophthalmology & Visual Science, 47(9), 3946-3950. https://doi.org/10.1167/iovs.06-0058

Interferon-a: a key factor in autoimmune disease? / Plskova, Jarka; Greiner, Kathrin; Muckersie, Elizabeth; Duncan, Linda; Forrester, John Vincent.

In: Investigative Ophthalmology & Visual Science, Vol. 47, No. 9, 09.2006, p. 3946-3950.

Research output: Contribution to journalArticle

Plskova, J, Greiner, K, Muckersie, E, Duncan, L & Forrester, JV 2006, 'Interferon-a: a key factor in autoimmune disease?', Investigative Ophthalmology & Visual Science, vol. 47, no. 9, pp. 3946-3950. https://doi.org/10.1167/iovs.06-0058
Plskova J, Greiner K, Muckersie E, Duncan L, Forrester JV. Interferon-a: a key factor in autoimmune disease? Investigative Ophthalmology & Visual Science. 2006 Sep;47(9):3946-3950. https://doi.org/10.1167/iovs.06-0058
Plskova, Jarka ; Greiner, Kathrin ; Muckersie, Elizabeth ; Duncan, Linda ; Forrester, John Vincent. / Interferon-a: a key factor in autoimmune disease?. In: Investigative Ophthalmology & Visual Science. 2006 ; Vol. 47, No. 9. pp. 3946-3950.
@article{da318de2c19a451098903c7f016a2ec1,
title = "Interferon-a: a key factor in autoimmune disease?",
abstract = "PURPOSE. Interferon (IFN)-alpha is an effective drug for treatment of uveitis in Behcet's disease. This study was undertaken to investigate the mechanism of action of IFN-alpha in the treatment of various types of noninfectious sight-threatening uveitis.METHODS. Eleven patients with refractory uveitis, and 13 healthy individuals were enrolled. The number of circulating plasmacytoid dendritic cells (pDCs) and their capacity to produce IFN-alpha in culture on stimulation with synthetic oligodinucleotides containing the CpG-motif were studied. Peripheral blood CD4(+) T-cell phenotype and activation status were evaluated by flow cytometry at 0, 2, and 8 weeks after treatment for expression of CD69, CD62L, chemokine receptors (CCR4, CXCR3, and CCR5), and intracellular cytokines (TNF-alpha, IFN-gamma, and IL-10).RESULTS. All patients experienced a positive clinical response to IFN-alpha treatment. There was no significant difference between patients and control subjects in the number of circulating pDCs, but there was a significant decrease in the capability of patients' pDCs to produce IFN-alpha in response to CpG (P < 0.001). Peripheral blood CD4(+) T cells expressed reduced levels of surface CD62L (P < 0.005) as a measure of activation and higher levels of chemokine receptors CXCR3, CCR4, and CCR5 (P < 0.005, P < 0.05, and P < 0.05, respectively); in addition, intracellular T-cell IL-10 levels were increased once the treatment was initiated (P < 0.01).CONCLUSIONS. The data suggest that IFN-alpha may control uveitis by promoting induction of IL-10-producing T-cells, possibly T-regulatory cells. Dysregulation of the T-cell population in patients with uveitis may be associated with a defect in the pDCs' ability to produce IFN-alpha, which can be circumvented with administration of exogenous IFN-alpha.",
keywords = "PLASMACYTOID DENDRITIC CELLS, CD4(+) T-CELLS, IFN-ALPHA, TNF-ALPHA, ANTIRETROVIRAL THERAPY, PERIPHERAL-BLOOD, I INTERFERON, ACTIVATION, INDUCTION, UVEITIS",
author = "Jarka Plskova and Kathrin Greiner and Elizabeth Muckersie and Linda Duncan and Forrester, {John Vincent}",
year = "2006",
month = "9",
doi = "10.1167/iovs.06-0058",
language = "English",
volume = "47",
pages = "3946--3950",
journal = "Investigative Ophthalmology & Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "9",

}

TY - JOUR

T1 - Interferon-a: a key factor in autoimmune disease?

AU - Plskova, Jarka

AU - Greiner, Kathrin

AU - Muckersie, Elizabeth

AU - Duncan, Linda

AU - Forrester, John Vincent

PY - 2006/9

Y1 - 2006/9

N2 - PURPOSE. Interferon (IFN)-alpha is an effective drug for treatment of uveitis in Behcet's disease. This study was undertaken to investigate the mechanism of action of IFN-alpha in the treatment of various types of noninfectious sight-threatening uveitis.METHODS. Eleven patients with refractory uveitis, and 13 healthy individuals were enrolled. The number of circulating plasmacytoid dendritic cells (pDCs) and their capacity to produce IFN-alpha in culture on stimulation with synthetic oligodinucleotides containing the CpG-motif were studied. Peripheral blood CD4(+) T-cell phenotype and activation status were evaluated by flow cytometry at 0, 2, and 8 weeks after treatment for expression of CD69, CD62L, chemokine receptors (CCR4, CXCR3, and CCR5), and intracellular cytokines (TNF-alpha, IFN-gamma, and IL-10).RESULTS. All patients experienced a positive clinical response to IFN-alpha treatment. There was no significant difference between patients and control subjects in the number of circulating pDCs, but there was a significant decrease in the capability of patients' pDCs to produce IFN-alpha in response to CpG (P < 0.001). Peripheral blood CD4(+) T cells expressed reduced levels of surface CD62L (P < 0.005) as a measure of activation and higher levels of chemokine receptors CXCR3, CCR4, and CCR5 (P < 0.005, P < 0.05, and P < 0.05, respectively); in addition, intracellular T-cell IL-10 levels were increased once the treatment was initiated (P < 0.01).CONCLUSIONS. The data suggest that IFN-alpha may control uveitis by promoting induction of IL-10-producing T-cells, possibly T-regulatory cells. Dysregulation of the T-cell population in patients with uveitis may be associated with a defect in the pDCs' ability to produce IFN-alpha, which can be circumvented with administration of exogenous IFN-alpha.

AB - PURPOSE. Interferon (IFN)-alpha is an effective drug for treatment of uveitis in Behcet's disease. This study was undertaken to investigate the mechanism of action of IFN-alpha in the treatment of various types of noninfectious sight-threatening uveitis.METHODS. Eleven patients with refractory uveitis, and 13 healthy individuals were enrolled. The number of circulating plasmacytoid dendritic cells (pDCs) and their capacity to produce IFN-alpha in culture on stimulation with synthetic oligodinucleotides containing the CpG-motif were studied. Peripheral blood CD4(+) T-cell phenotype and activation status were evaluated by flow cytometry at 0, 2, and 8 weeks after treatment for expression of CD69, CD62L, chemokine receptors (CCR4, CXCR3, and CCR5), and intracellular cytokines (TNF-alpha, IFN-gamma, and IL-10).RESULTS. All patients experienced a positive clinical response to IFN-alpha treatment. There was no significant difference between patients and control subjects in the number of circulating pDCs, but there was a significant decrease in the capability of patients' pDCs to produce IFN-alpha in response to CpG (P < 0.001). Peripheral blood CD4(+) T cells expressed reduced levels of surface CD62L (P < 0.005) as a measure of activation and higher levels of chemokine receptors CXCR3, CCR4, and CCR5 (P < 0.005, P < 0.05, and P < 0.05, respectively); in addition, intracellular T-cell IL-10 levels were increased once the treatment was initiated (P < 0.01).CONCLUSIONS. The data suggest that IFN-alpha may control uveitis by promoting induction of IL-10-producing T-cells, possibly T-regulatory cells. Dysregulation of the T-cell population in patients with uveitis may be associated with a defect in the pDCs' ability to produce IFN-alpha, which can be circumvented with administration of exogenous IFN-alpha.

KW - PLASMACYTOID DENDRITIC CELLS

KW - CD4(+) T-CELLS

KW - IFN-ALPHA

KW - TNF-ALPHA

KW - ANTIRETROVIRAL THERAPY

KW - PERIPHERAL-BLOOD

KW - I INTERFERON

KW - ACTIVATION

KW - INDUCTION

KW - UVEITIS

U2 - 10.1167/iovs.06-0058

DO - 10.1167/iovs.06-0058

M3 - Article

VL - 47

SP - 3946

EP - 3950

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 9

ER -