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In Vitro Differentiation of Naive CD4+ T Cells into Pathogenic Th17 Cells in Mouse
Published on: October 25, 2024
Phenotypic and functional features of human Th17 cells.
Francesco Annunziato1, Lorenzo Cosmi, Veronica Santarlasci
1Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders (DENOTHE), University of Florence, Florence 50134, Italy.
The Journal of Experimental Medicine
|July 20, 2007
Summary
This study identifies T helper 17 (Th17) cells and a dual T helper 17/T helper 1 (Th17/Th1) subset in Crohn's disease patients. These cells exhibit unique markers and functions, offering insights into autoimmune disorders.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- T helper (Th) 17 cells are crucial for immunity but implicated in autoimmune diseases.
- Human Th17 cell properties remain incompletely understood, particularly in inflammatory conditions like Crohn's disease.
Purpose of the Study:
- To characterize human Th17 cells and identify potential subsets involved in Crohn's disease pathogenesis.
- To investigate the functional and molecular features of Th17 cells and a novel Th17/Th1 subset.
Main Methods:
- Analysis of gut-infiltrating CD4+ T cells from Crohn's disease patients.
- Flow cytometry and gene expression analysis to identify cell surface markers and transcription factors (IL-23R, CCR6, ROR gamma t, T-bet).
- Functional assays assessing cytokine production (IL-17, IFN-gamma) and regulatory T cell susceptibility.
Main Results:
- Demonstrated the presence of Th17 and Th17/Th1 cells in the gut of Crohn's disease patients.
- Both subsets selectively expressed IL-23R, CCR6, and ROR gamma t, with similar functional characteristics.
- Identified a Th17/Th1 subset expressing T-bet; IL-12 stimulation modulated Th17 cells towards IFN-gamma production, down-regulating IL-17.
Conclusions:
- Selective markers for human Th17 cells were identified, aiding in understanding their role in disease.
- A subset of cells sharing Th1 and Th17 features was discovered, suggesting plasticity and potential developmental links between Th17 and Th1 cells.
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