We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
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.
- Authors
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
- 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 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.
- Subjects
IMMUNE response; T cells; T-cell exhaustion; GENE expression; CELL physiology
- Publication
Journal of Leukocyte Biology, 2024, Vol 115, Issue 6, p1108
- ISSN
0741-5400
- Publication type
Article
- DOI
10.1093/jleuko/qiae034