Open AccessCell Surface Galectin-9 Expressing Th Cells Regulate Th17 and Foxp3+ Treg Development by Galectin-9 Secretion
Author(s) -
Souichi Oomizu,
Tomohiro Arikawa,
Toshiro Niki,
Takeshi Kadowaki,
Masaki Ueno,
Nozomu Nishi,
Akira Yamauchi,
Toshio Hattori,
Tsutomu Masaki,
Mitsuomi Hirashima
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0048574
Subject(s) - microbiology and biotechnology , secretion , galectin , foxp3 , biology , il 2 receptor , galectin 3 , galectin 1 , immune system , t cell , immunology , biochemistry
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.