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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Cell surface galectin-9 expressing Th cells regulate Th17 and Foxp3+ Treg development by galectin-9 secretion
Souichi Oomizu1, Tomohiro Arikawa, Toshiro Niki
1Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Plos One
|November 13, 2012
Summary
Certain CD4 T cells secrete Galectin-9 (Gal-9) upon stimulation, regulating immune responses. These Gal-9-secreting T helper (Th) cells play a conserved role in immunity, offering potential for disease treatment.
Area of Science:
- Immunology
- Cell Biology
- Molecular Medicine
Background:
- Galectin-9 (Gal-9) is a mammalian lectin that modulates immune responses by influencing T helper 17 (Th17) and regulatory T cells (Tregs).
- Gal-9's intracellular localization and lack of a signal peptide raise questions about its secretion mechanism and the identity of Gal-9-secreting cells in vivo.
- Cell surface expression of Gal-9 does not always correlate with its secretion, making in vivo identification challenging.
Purpose of the Study:
- To identify the specific CD4 T cells responsible for Gal-9 secretion in vivo.
- To investigate the mechanism and function of Gal-9 secretion by identified T cells.
- To explore the evolutionary conservation and potential therapeutic applications of these Gal-9-secreting cells.
Main Methods:
- T cell receptor (TCR) stimulation assays were used to investigate Gal-9 secretion from CD4 T cells.
- Flow cytometry and intracellular cytokine staining were employed to characterize Gal-9-expressing and secreting T cells.
- Co-culture experiments with Gal-9-secreting T cells and assessment of Th17/Treg balance were performed.
- Gal-9 antagonist, IL-10, and TGF-β blockade experiments were conducted to elucidate the secretion mechanism.
Main Results:
- CD4 T cells expressing Gal-9 on their surface (Gal-9(+) Th cells) were identified as the primary secretors of Gal-9 upon TCR stimulation.
- These Gal-9(+) Th cells secreted Gal-9 independently of their intracellular Gal-9 levels and did not express Foxp3, but produced IL-10 and TGF-β.
- In co-cultures, Gal-9(+) Th cells modulated Th17/Treg differentiation similarly to exogenous Gal-9, with regulation dependent on Gal-9 itself, not IL-10 or TGF-β.
- Human CD4 T cells exhibited similar Gal-9 secretion patterns, indicating evolutionary conservation.
Conclusions:
- Specific CD4 T cells (Gal-9(+) Th cells) secrete Gal-9 upon TCR stimulation, clarifying a key mechanism of Gal-9 regulation in immune responses.
- These findings reveal a novel pathway for Gal-9-mediated immune modulation that is distinct from its intracellular functions.
- The conserved role of Gal-9(+) Th cells suggests their potential utility as diagnostic markers or therapeutic targets for immunological diseases.
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