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Author Spotlight: Achieving High-Purity In Vitro Differentiation of Th17 Cells Using Cytokine Concentration Modulation
Published on: October 25, 2024
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The protease cathepsin L regulates Th17 cell differentiation
Lifei Hou1, Jessica Cooley2, Richard Swanson3
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Journal of Autoimmunity
|September 8, 2015
Summary
The protease cathepsin L (catL) promotes T helper 17 (Th17) cell differentiation. Serine protease inhibitor B1 (serpinB1) and asparagine endopeptidase (AEP) regulate catL activity, offering a therapeutic target for autoimmune disorders.
Area of Science:
- Immunology
- Cell Biology
- Protease Biology
Background:
- Increased IL-17(+) T cells observed in serpinB1-deficient mice.
- Serine protease inhibitor B1 (serpinB1) deficiency impacts T helper 17 (Th17) cell differentiation.
- Proteases may play a role in promoting Th17 cell differentiation.
Purpose of the Study:
- Investigate the role of proteases in Th17 cell differentiation.
- Identify specific proteases involved in Th17 cell development.
- Explore the regulatory mechanism of Th17 cell differentiation involving serpinB1.
Main Methods:
- Analysis of T helper 17 (Th17) cell differentiation in serpinB1-deficient mice.
- Assay of cathepsin L (catL) activity and forms in Th17 cells.
- Inhibition studies using broad and selective cathepsin inhibitors, and asparagine endopeptidase (AEP) inhibitors.
Main Results:
- Cathepsin L (catL) is induced in Th17 cells and promotes their differentiation.
- Single-chain catL is biologically active in Th17 generation.
- SerpinB1 and AEP regulate catL activity and Th17 cell generation.
Conclusions:
- Th17 cell differentiation is actively regulated by a cathepsin L-serpinB1-AEP module.
- This protease regulatory module represents a potential therapeutic target for Th17 cell-driven autoimmune diseases.
