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Differential requirement for IL-2 and IL-23 in the differentiation and effector functions of Th17/ILC3-like cells in a human T cell line
- Source :
- Journal of Leukocyte Biology; June 2024, Vol. 115 Issue: 6 p1108-1117, 10p
- Publication Year :
- 2024
-
Abstract
- A well-documented Achilles heel of current cancer immunotherapy approaches is T cell exhaustion within solid tumor tissues. The proinflammatory cytokine interleukin (IL)-23 has been utilized to augment chimeric antigen receptor (CAR) T cell survival and tumor immunity. However, in-depth interrogation of molecular events downstream of IL-23/IL-23 receptor signaling is hampered by a paucity of suitable cell models. The current study investigates the differential contribution of IL-2 and IL-23 to the maintenance and differentiation of the IL-23 responsive Kit225 T-cell line. We observed that IL-23 enhanced cellular fitness and survival but was insufficient to drive proliferation. IL-23 rapidly induced phosphorylation of STAT1, STAT3, and STAT4, and messenger RNA expression of IL17A, the archetypal effector cytokine of T helper 17 (Th17) cells, but not their lineage markers RORCand NCR1. These observations suggest that IL-23 endowed Th17/ILC3-like effector function but did not promote their differentiation. In contrast, spontaneous differentiation of Kit225 cells toward a Th17/ILC3-like phenotype was induced by prolonged IL-2 withdrawal. This was marked by strongly elevated basal IL17Aand IL17Fexpression and the secretion of IL-17. Together, our data present Kit225 cells as a valuable model for studying the interplay between cytokines and their contribution to T cell survival, proliferation, and differentiation.IL-2 maintained Kit225 cells in a proliferative and undifferentiated state. Its withdrawal initiated their spontaneous differentiation into a Th17/ILC3-like phenotype.
Details
- Language :
- English
- ISSN :
- 07415400 and 19383673
- Volume :
- 115
- Issue :
- 6
- Database :
- Supplemental Index
- Journal :
- Journal of Leukocyte Biology
- Publication Type :
- Periodical
- Accession number :
- ejs66493268
- Full Text :
- https://doi.org/10.1093/jleuko/qiae034