title: Tim1 and Tim3 are not essential for experimental allergic asthma.
abstract: BACKGROUND
  Initial studies suggested that polymorphisms in Tim1 and Tim3 contribute to the development of airway hyperreactivity (AHR) in an acute mouse model of asthma. This was also mirrored in human genetic studies where polymorphisms in Tim1 and Tim3 have been associated with atopic populations.
  
  
  OBJECTIVE
  Further studies using anti-Tim1 or -Tim3 antibodies, or Tim fusion proteins, have also suggested that these molecules may function as regulators of type-1 and type-2 immunity. However, their role in the development of AHR and airway inflammation remains unclear. Given the proposed roles for Tim1 and Tim3 in type-1 and type-2 responses, we sought to determine whether these molecules were important in regulating antigen-driven lung allergy and inflammation.
  
  
  METHODS
  We used Tim1- and Tim3-deficient mice and determined how the development of allergic lung inflammation was affected.
  
  
  RESULTS
  AHR was induced normally in the absence of both Tim1 and Tim3, although Tim1-deficient mice did show a small but significant decrease in cell infiltration in the lung and blood eosinophilia. Although Tim3 was expressed on CD4(+) T cells in the allergic lung, Tim1 expression was restricted to CD86(+) B cells.
  
  
  CONCLUSIONS
  Thus, Tim1 and Tim3 are not essential for the induction of the type-2 response in lung allergy. This is contrary to what was proposed in a number of other studies using neutralizing and activating antibodies and questions the clinical relevance of Tim1 and Tim3 for novel allergy therapies.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK. jbarlow@mrc-lmb.cam.ac.uk
authors.forename: J L
authors.initials: JL
authors.lastname: Barlow
authors.forename: S H
authors.initials: SH
authors.lastname: Wong
authors.forename: S J
authors.initials: SJ
authors.lastname: Ballantyne
authors.forename: H E
authors.initials: HE
authors.lastname: Jolin
authors.forename: A N J
authors.initials: AN
authors.lastname: McKenzie
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008168:Lung; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011991:Receptors, Virus / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D051940:B7-2 Antigen; C442240:Havcr1 protein, mouse; C442241:Havcr2 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D011991:Receptors, Virus