title: Small interfering RNA targeting T-cell Ig mucin-3 decreases allergic airway inflammation and hyperresponsiveness.
abstract: Since CD4+ T cells play a pivotal role in the development of airway inflammation and hyperresponsiveness, targeting activated CD4+ T cell subsets and increasing the cells with regulatory function would be a logical therapeutic approach. We showed that this outcome can be achieved by local therapy with Tim-3, which is a negative regulator of CD4+ T cells. Tim-3 expression was up-regulated by ovalbumin (OVA) induction. Attenuating Tim-3 expression by RNA interference suppressed allergen-induced immune responses. Intranasal application of Tim-3 shRNA diminished airway inflammation and hyperresponsiveness. Multiple mechanisms were involved in the inhibitory effects, including regulation the imbalance of Th1/Th17 and increasing Treg cell expression. Our results indicate that the Tim-3 pathway is highly involved in the regulation of asthma. Targeting Tim-3 by siRNA may hold therapeutic potential in preventing the development of allergic asthma.
authors.affiliation: Department of pulmonary Medicine, Wuhan Women and Children Health Care Center, Wuhan, China. lusi74@163.com
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Lu
authors.forename: Karen S
authors.initials: KS
authors.lastname: McCoy
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Xu
authors.forename: Wei-Kun
authors.initials: WK
authors.lastname: Hu
authors.forename: He-Bin
authors.initials: HB
authors.lastname: Chen
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000628:therapy; D002478:Cells, Cultured; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D010047:Ovalbumin