title: Cell surface galectin-9 expressing Th cells regulate Th17 and Foxp3+ Treg development by galectin-9 secretion.
abstract: Galectin-9 (Gal-9), a β-galactoside binding mammalian lectin, regulates immune responses by reducing pro-inflammatory IL-17-producing Th cells (Th17) and increasing anti-inflammatory Foxp3(+) regulatory T cells (Treg) in vitro and in vivo. These functions of Gal-9 are thought to be exerted by binding to receptor molecules on the cell surface. However, Gal-9 lacks a signal peptide for secretion and is predominantly located in the cytoplasm, which raises questions regarding how and which cells secrete Gal-9 in vivo. Since Gal-9 expression does not necessarily correlate with its secretion, Gal-9-secreting cells in vivo have been elusive. We report here that CD4 T cells expressing Gal-9 on the cell surface (Gal-9(+) Th cells) secrete Gal-9 upon T cell receptor (TCR) stimulation, but other CD4 T cells do not, although they express an equivalent amount of intracellular Gal-9. Gal-9(+) Th cells expressed interleukin (IL)-10 and transforming growth factor (TGF)-β but did not express Foxp3. In a co-culture experiment, Gal-9(+) Th cells regulated Th17/Treg development in a manner similar to that by exogenous Gal-9, during which the regulation by Gal-9(+) Th cells was shown to be sensitive to a Gal-9 antagonist but insensitive to IL-10 and TGF-β blockades. Further elucidation of Gal-9(+) Th cells in humans indicates a conserved role of these cells through evolution and implies the possible utility of these cells for diagnosis or treatment of immunological diseases.
authors.affiliation: Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Oomizu
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arikawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Nozomu
authors.initials: N
authors.lastname: Nishi
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Hattori
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037161:Galectins; C105032:LGALS9 protein, human; D011948:Receptors, Antigen, T-Cell; C508186:galectin 9, mouse