| Autor: |
Sarah, Momtazkari, Anahita, Dev Choudhury, Zachary, Wei Ern Yong, Thanh, Dong Le, Hiep, Nguyen Canh, Kenichi, Harada, Hori, Toshiyuki, Motomi, Osato, Chiaki, Takahashi, Koh, Cai Ping, Dominic, Chih-Cheng Voon |
| Předmět: |
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| Zdroj: |
Journal of Leukocyte Biology; Jun2024, Vol. 115 Issue 6, p1108-1117, 10p |
| Abstrakt: |
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 RORC and 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 IL17A and IL17F expression 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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