Abstract
Abstract Ocular HSV-1 infection can cause a blinding CD4+ T cell orchestrated immunoinflammatory lesion called Stromal Keratitis (SK). Lesion severity is affected by the balance of proinflammatory effector T and regulatory T cells (Treg). In this report we show that expanding Treg activity using TCDD (2, 3, 7, 8- Tetrachlorodibenzo-p-dioxin), a ligand for the AhR receptor, results in the differential expansion of Treg in the eye and a resultant reduction in the extent of inflammatory lesions. Treatment of HSV infected mice with TCDD either on day 1 or day 5 pi, diminished the severity of SK lesions as well as the extent of corneal angiogenesis. The observed effect was mainly due to the changed balance of CD4+ T cells in the cornea that were IFN-γ or IL17 cytokine producers compared to those that were Foxp3+ Tregs. The change was explained by the significantly increased apoptosis of activated effector T cells but not of Tregs. Additionally, effector T cells from HSV infected mice proliferated significantly less in TCDD treated mice compared to control mice. Furthermore the addition of TCDD to the culture of antiCD3/CD28 stimulated naïve CD4+ T cells caused significant induction of Tregs. In conclusion, our results demonstrate that modulation of AhR signaling by TCDD represents a valuable approach to expand Treg and inhibit Th1 and Th17 cells to control HSV induced blinding lesions.
Published Version
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