Controlling viral immuno-inflammatory lesions by modulating aryl hydrocarbon receptor signaling

Ocular herpes simplex virus infection can cause a blinding cd4 + t cell orchestrated immuno-inflammatory lesion in the cornea called stromal keratitis (sk). a key to controlling the severity of sk lesions is to suppress the activity of t cells that orchestrate lesions and enhance the representation of regulatory cells that inhibit effector cell function. in this report we show that a single administration of tcdd (2,3,7,8- tetrachlorodibenzo-p-dioxin),a non-physiological ligand for the ahr receptor,was an effective means of reducing the severity of sk lesions. it acted by causing apoptosis of foxp3 - cd4 + t cells but had no effect on foxp3 + cd4 + tregs. tcdd also decreased the proliferation of foxp3 - cd4 + t cells. the consequence was an increase in the ratio of tregs to t effectors which likely accounted for the reduced inflammatory responses. in addition,in vitro studies revealed that tcdd addition to anti-cd3/cd28 stimulated naïve cd4 + t cells caused a significant induction of tregs,but inhibited the differentiation of th1 and th17 cells. since a single tcdd administration given after the disease process had been initiated generated long lasting anti-inflammatory effects,the approach holds promise as a therapeutic means of controlling virus induced inflammatory lesions. © 2011 veiga-parga,et al.