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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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Cell-autonomous Hedgehog signaling controls Th17 polarization and pathogenicity.
Joachim Hanna1, Flavio Beke1, Louise M O'Brien1
1Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
Nature Communications
|July 14, 2022
Summary
Hedgehog signaling selectively drives T helper 17 (Th17) cell polarization, a key factor in autoimmune diseases. Inhibiting this pathway reduces intestinal inflammation, suggesting potential therapies for inflammatory bowel disease.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- T helper 17 (Th17) cells are critical in autoimmune diseases.
- Signaling pathways governing Th17 cell differentiation remain largely unknown.
- Hedgehog signaling is crucial for embryonic development and tissue patterning.
Purpose of the Study:
- To investigate the role of Hedgehog signaling in Th17 cell polarization.
- To determine the mechanisms by which Hedgehog signaling influences Th17 cells.
- To evaluate the therapeutic potential of Hedgehog pathway inhibitors in inflammatory bowel disease.
Main Methods:
- Investigated cell-autonomous Hedgehog signaling in Th17 cell polarization.
- Utilized Gli3 and AMPK pathways for Hedgehog signaling activation.
- Employed vismodegib (Hedgehog inhibitor) and genetic ablation of Ihh in CD4+ T cells.
- Assessed disease severity in mouse models of intestinal inflammation.
- Analyzed Hedgehog pathway and Th17 marker expression in human ulcerative colitis tissue.
Main Results:
- Cell-autonomous Hedgehog signaling selectively promotes Th17 polarization, independent of external ligands.
- Endogenous Ihh activates canonical and non-canonical Hedgehog pathways via Gli3 and AMPK.
- Hedgehog pathway inhibition significantly reduced disease severity in experimental intestinal inflammation.
- Upregulated Hedgehog pathway expression in human ulcerative colitis correlates with Th17 markers.
Conclusions:
- Hedgehog signaling is implicated in Th17 cell polarization and intestinal immunopathology.
- Targeting Hedgehog signaling with inhibitors shows therapeutic promise for inflammatory bowel disease.
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