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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
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Activated CLL cells regulate IL-17F-producing Th17 cells in miR155-dependent and outcome-specific manners
Byeongho Jung1,2, Gerardo Ferrer1, Pui Yan Chiu3
1Karches Center for Oncology Research, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA.
JCI Insight
|May 5, 2022
Summary
Chronic lymphocytic leukemia (CLL) involves T cells. CLL cells promote miR155 expression in T cells, enhancing IL-17F+ Th17 generation, which correlates with better patient outcomes.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Chronic lymphocytic leukemia (CLL) is a B cell malignancy dependent on cellular interactions.
- Elevated circulating IL-17A+ and IL-17F+ CD4+ T (Th17) cells are observed in CLL patients, with higher IL-17A+ Th17 counts indicating better prognosis.
Purpose of the Study:
- To investigate the role of miR155 in Th17 cell differentiation in CLL.
- To determine if CLL cells directly influence T cell miR155 levels and subsequent Th17 differentiation.
- To explore the correlation between T cell miR155 expression changes and clinical outcomes in CLL.
Main Methods:
- Comparative analysis of miR155 expression in Th17 cells from CLL patients and healthy controls.
- Co-culture experiments involving naive CD4+ T (Tn) cells and resting or activated (Bact) CLL cells.
- Assessment of IL-17A and IL-17F production following miR155 modulation and co-culture.
- Correlation analysis between T cell miR155 expression changes, IL-17F production, and clinical outcomes, including IGHV mutation status.
Main Results:
- CLL Th17 cells exhibit higher miR155 expression compared to control Th17 cells, despite similar basal miR155 levels in naive T cells.
- Co-culturing Tn cells with CLL Bact cells alters T cell miR155 levels and promotes IL-17A+ and IL-17F+ T cell generation via an miR155-dependent pathway.
- miR155 inhibition blocks CLL Bact cell-induced Th17 generation.
- Changes in Tn cell miR155 expression correlate linearly with IL-17F production and clinical outcomes, independent of IGHV mutation status.
Conclusions:
- CLL cells can upregulate miR155 expression in naive T cells, enhancing the generation of IL-17F+ Th17 cells.
- This CLL-mediated mechanism, involving miR155 and IL-17F+ Th17 cells, is associated with favorable clinical courses in CLL patients.
- Identifies a novel CLL-dependent pathway influencing T cell differentiation and patient prognosis.
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