title: TIM-3 is not essential for development of airway inflammation induced by house dust mite antigens.
abstract: BACKGROUND
  T cell immunoglobulin domain and mucin domain-containing molecule 3 (TIM-3), which is preferentially expressed on Th1 cells rather than Th2 cells, is considered to be a negative regulator of Th1 cell function. This suggests that TIM-3 indirectly enhances Th2-type immune responses by suppressing Th1 cell function.
  
  
  METHODS
  To investigate TIM-3's possible involvement in Th2-type acute and chronic airway inflammation, wild-type and TIM-3-deficient (TIM-3-/-) mice were sensitized and challenged with a house dust mite (HDM) extract. Airway inflammation and the number of inflammatory cells in bronchoalveolar lavage fluids (BALFs) in the mice were determined by histological analysis and with a hemocytometer, respectively. Expression of mRNA in the lungs was determined by quantitative PCR, while the levels of cytokines in the BALFs and IgE in sera were determined by ELISA.
  
  
  RESULTS
  Despite constitutive expression of TIM-3 mRNA in the lungs, the number of eosinophils in bronchoalveolar lavage fluids (BALFs) and the score of pulmonary inflammation were comparable between wild-type and TIM-3-/-mice during both acute and chronic HDM-induced airway inflammation. On the other hand, the number of lymphocytes in the BALFs of TIM-3-/-mice was significantly increased compared with wild-type mice during HDM-induced chronic, but not acute, airway inflammation, while the levels of Th2 cytokines in the BALFs and HDM-specific IgG1 and IgG2a and total IgE in the sera were comparable in both groups.
  
  
  CONCLUSIONS
  Our findings indicate that, in mice, TIM-3 is not essential for development of HDM-induced acute or chronic allergic airway inflammation, although it appears to be involved in reduced lymphocyte recruitment during HDM-induced chronic allergic airway inflammation.
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hiraishi
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Nambu
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Medical Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shibui
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Nakanishi
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Iikura
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Animal Research Center, Tokyo Medical University, Tokyo, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan. Electronic address: snakae@ims.u-tokyo.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines; D004195:Disease Models, Animal; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000235:genetics*; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012140:Respiratory Tract Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D007073:Immunoglobulin E
keywords: Allergy; Asthma; House dust mite; Mouse; TIM-3