title: Interleukin-17 enhanced immunoinflammatory lesions in a mouse model of recurrent herpetic keratitis.
abstract: Interleukin-17 (IL-17), mainly produced by activated (memory) T cells, has been found in the corneas from herpetic stromal keratitis (HSK) patients. To better understand the role of IL-17 and to optimize fidelity to human recurrent HSK, in this study, we utilized a mouse model of recurrent HSK, examined the expression of IL-17 and Th17 cells, and determine the alterability of virus-induced corneal inflammation after anti-IL-17 antibody treatment during murine recurrent HSK. We found that Th17 cells were obviously up-regulated in both cornea and DLNs of recurrent mice. Peak IL-17 protein present in recurrent cornea in conjunction with peak opacity mediated by CD4(+) T cells. Systemic administration of anti-IL-17 antibody resulted in a diminished severity of corneal opacity, neovascularization, and CD4(+) T cells infiltration compared to control. Anti-IL-17 treatment down-regulated the mRNA and protein levels of TNF-α expression in recurrent corneas, and decreased HSV-specific DTH responses. Our results indicate that elevated IL-17 expression may be involved in the development of recurrent HSK. The likely mechanisms of action for IL-17 are through up-regulating TNF-α expression and promoting HSV-specific DTH responses. Thus, IL-17 might constitute a useful target for therapeutic intervention in recurrent HSK.
authors.affiliation: Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, People's Republic of China. xialk@sj-hospital.org
authors.forename: Likun
authors.initials: L
authors.lastname: Xia
authors.forename: Shengnan
authors.initials: S
authors.lastname: Zhang
authors.forename: Zheyao
authors.initials: Z
authors.lastname: Cao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yang
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D002522:Chlorocebus aethiops; D003315:Cornea / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016510:Corneal Neovascularization / Q000276:immunology / Q000473:pathology / Q000821:virology; D003318:Corneal Opacity / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007249:Inflammation / Q000473:pathology / Q000821:virology; D020381:Interleukin-17 / Q000276:immunology*; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055502:Secondary Prevention; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014775:Virus Activation; D017201:Virus Shedding
chemical_list: D000906:Antibodies; D020381:Interleukin-17; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha