Retinal cells suppress intraocular inflammation (uveitis) through production of interleukin-27 and interleukin-10.
Summary of "Retinal cells suppress intraocular inflammation (uveitis) through production of interleukin-27 and interleukin-10."
Neuronal or photoreceptor deficit observed in uveitis and multiple sclerosis derives in part from inability to control inflammatory responses in neuroretina or brain. Recently, IL-27 was found to play a role in suppressing experimental autoimmune uveitis and experimental autoimmune encephalomyelitis, two animal models that share essential pathological features of human uveitis and multiple sclerosis, respectively. However, the mechanism by which interleukin-27 (IL-27) inhibits central nervous system (CNS) inflammation is not clear. In this study we have investigated mechanisms that mitigate or curtail intraocular inflammation (uveitis) and examined whether inhibitory effects of IL-27 are mediated locally by neuroretinal cells or by regulatory T cells. We show here that microglia cells in the neuroretina constitutively secrete IL-27 and its expression is up-regulated during uveitis. We further show that photoreceptors constitutively express IL-27 receptor and respond to IL-27 signalling by producing anti-inflammatory molecules, IL-10 and suppressor of cytokine signalling 1 (SOCS1) through signal transducer and activator of transcription 1 (STAT1) -dependent mechanisms. Moreover, STAT1-deficient mice produced reduced amounts of IL-27, IL-10 and SOCS1 and developed more severe uveitis. Surprisingly, IL-10-producing regulatory T cells had marginal roles in suppressing uveitis. These results suggest that suppression of intraocular inflammation might be mediated through endogenous production of IL-27 and IL-10 by retinal cells, whereas SOCS proteins induced by IL-27 during uveitis may function to protect the neuroretinal cells from the toxic effects of pro-inflammatory cytokines. Targeted delivery of IL-27 into immune privileged tissues of the CNS may therefore be beneficial in the treatment of CNS inflammatory diseases, such as uveitis and multiple sclerosis.
Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21294722
- DOI: http://dx.doi.org/10.1111/j.1365-2567.2010.03379.x
Medical and Biotech [MESH] Definitions
Abnormally low intraocular pressure often related to chronic inflammation (uveitis).
Retinal Bipolar Cells
INTERNEURONS of the vertebrate RETINA containing two processes. They receive inputs from the RETINAL PHOTORECEPTOR CELLS and send outputs to the RETINAL GANGLION CELLS. The bipolar cells also make lateral connections in the retina with the RETINAL HORIZONTAL CELLS and with the AMACRINE CELLS.
Specialized ophthalmic technique used in the surgical repair and or treatment of disorders that include retinal tears or detachment; MACULAR HOLES; hereditary retinal disease; AIDS-related retinal infections; ocular tumors; MACULAR DEGENERATION; DIABETIC RETINOPATHY; and UVEITIS.
Inflammation of the anterior uvea comprising the iris, angle structures, and the ciliary body. Manifestations of this disorder include ciliary injection, exudation into the anterior chamber, iris changes, and adhesions between the iris and lens (posterior synechiae). Intraocular pressure may be increased or reduced.
Retinal Horizontal Cells
NEURONS in the inner nuclear layer of the RETINA that synapse with both the RETINAL PHOTORECEPTOR CELLS and the RETINAL BIPOLAR CELLS, as well as other horizontal cells. The horizontal cells modulate the sensory signal.
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