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In Vitro Differentiation of Naive CD4+ T Cells into Pathogenic Th17 Cells in Mouse
Published on: October 25, 2024
Th17 cells: a new fate for differentiating helper T cells
1Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, Musculoskeletal and Skin Diseases, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. zchen@utu.fi
Immunologic Research
|January 4, 2008
Summary
A new T helper 17 (Th17) cell lineage, distinct from Th1 and Th2 cells, produces inflammatory cytokines and plays a key role in host defense and autoimmune diseases. Targeting Th17 cells shows promise for treating inflammatory conditions.
Area of Science:
- Immunology
- Cell Biology
Background:
- Traditionally, CD4(+) T helper cells were classified as Th1 or Th2 lineages.
- The role of Th1 cells and IFN-gamma in autoimmunity was questioned due to conflicting evidence.
Purpose of the Study:
- To characterize a newly identified lineage of helper T cells, designated Th17 cells.
- To investigate the role of Th17 cells in host defense and autoimmune pathogenesis.
Main Methods:
- Characterization of Th17 cell differentiation pathways in mouse and human systems.
- Analysis of cytokines produced by Th17 cells, including IL-17, IL-21, and IL-22.
- Investigation of signaling pathways involving TGFbeta-1, IL-6, IL-21, IL-23, and Stat3.
Main Results:
- Th17 cells selectively produce proinflammatory cytokines IL-17, IL-21, and IL-22.
- Mouse Th17 differentiation is induced by TGFbeta-1, IL-6, and IL-21, requiring Stat3 activation and RORgammat expression.
- IL-23 maintains Th17 cells in vivo; human Th17 differentiation is promoted by IL-1, IL-6, and IL-23, independent of TGFbeta-1.
Conclusions:
- Th17 cells are crucial for host defense against bacteria and fungi.
- Th17 cells are implicated in the pathogenesis of autoimmune diseases.
- Targeting the Th17 lineage offers a potential therapeutic strategy for inflammatory and autoimmune disorders.
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