title: Tim-1 regulates Th2 responses in an airway hypersensitivity model.
abstract: T-cell immunoglobulin mucin-1 (Tim-1) is a transmembrane protein postulated to be a key regulator of Th2-type immune responses. This hypothesis is based in part upon genetic studies associating Tim-1 polymorphisms in mice with a bias toward airway hyperrespon-siveness (AHR) and the development of Th2-type CD4(+)  T cells. Tim-1 expressed by Th2 CD4(+)  T cells has been proposed to function as a co-stimulatory molecule. Tim-1 is also expressed by B cells, macrophages, and dendritic cells, but its role in responses by these cell types has not been firmly established. Here, we generated Tim-1-deficient mice to determine the role of Tim-1 in a murine model of allergic airway disease that depends on the development and function of Th2 effector cells and results in the generation of AHR. We found antigen-driven recruitment of inflammatory cells into airways is increased in Tim-1-deficient mice relative to WT mice. In addition, we observed increased antigen-specific cytokine production by splenocytes from antigen-sensitized Tim-1-deficient mice relative to those from controls. These data support the conclusion that Tim-1 functions in pathways that suppress recruitment of inflammatory cells into the airways and the generation or activity of CD4(+)  T cells.
authors.affiliation: University of Iowa Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Curtiss
authors.forename: Jacob V
authors.initials: JV
authors.lastname: Gorman
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Businga
authors.forename: Geri
authors.initials: G
authors.lastname: Traver
authors.forename: Melody
authors.initials: M
authors.lastname: Singh
authors.forename: David K
authors.initials: DK
authors.lastname: Meyerholz
authors.forename: Joel N
authors.initials: JN
authors.lastname: Kline
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: John D
authors.initials: JD
authors.lastname: Colgan
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rothman
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Cassel
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000072596:Hepatitis A Virus Cellular Receptor 1; D018793:Interleukin-13 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D018793:Interleukin-13; D020381:Interleukin-17; D015848:Interleukin-5; D008565:Membrane Proteins