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Jun Chen, Weiwei Wang, Zilin Chen, Hongyan Zhou, Eric F Wawrousek, Igal Gery, Rachel R Caspi; Interferon beta modulates immune-mediated retinal inflammation by impairing T-cell trafficking. Invest. Ophthalmol. Vis. Sci. 2017;58(8):547. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Interferon (IFN)-beta can possess immunomodulatory functions in immune-mediated disorders and has been widely used in treating diseases such as multiple sclerosis. Yet, the underlying mechanisms of action of this cytokine remain largely unknown. In this study we examined the molecular mechanism by which IFN-beta exerts its immunomodulatory actions in autoimmune inflammatory eye disease driven by either Th1 or Th17 effector responses.
Ocular inflammation was induced in hen egg lysozyme (HEL) transgenic mice expressing HEL in their eyes by adoptive transfer of in vitro polarized Th1 or Th17 cells expressing HEL-specific T cell receptor (TCR). We tracked the transferred cells by their expression of 1G12, a clonotypic antibody against HEL-specific TCR. Treatment with IFN-beta was performed by daily intraperitoneal administration.
Treatment with IFN-beta suppressed the development of ocular inflammation in recipients of both types of cells, but did so by two different mechanisms. In recipients of Th-17 cells the treatment reduced the proportion of pathogenic Th17 cells and their RORγt expression in the spleen and in the eyes. In recipients of Th1 cells, however, treatment with IFN-beta enhanced expression of CXCL10/CXCL11/ICAM in spleen vascular epithelial cells, and consequently, sequestered the pathogenic Th1 cells in the spleen, resulting in fewer T-cell infiltrating the recipient eyes.
Our data demonstrate two different modes of action by IFN-beta in inhibition of immune-mediated inflammation induced by Th1 or Th17 lymphocytes. Of particular interest is the inhibition of inflammation by IFN-beta modulation of Th1 trafficking, representing a novel mode of action by an immunosuppressive cytokine.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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