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- Title
TCF-1 Is Required for CD4 T Cell Persistence Functions during AlloImmunity.
- Authors
Mammadli, Mahinbanu; Suo, Liye; Sen, Jyoti Misra; Karimi, Mobin
- Abstract
The transcription factor T cell factor-1 (TCF-1) is encoded by Tcf7 and plays a significant role in regulating immune responses to cancer and pathogens. TCF-1 plays a central role in CD4 T cell development; however, the biological function of TCF-1 on mature peripheral CD4 T cell-mediated alloimmunity is currently unknown. This report reveals that TCF-1 is critical for mature CD4 T cell stemness and their persistence functions. Our data show that mature CD4 T cells from TCF-1 cKO mice did not cause graft versus host disease (GvHD) during allogeneic CD4 T cell transplantation, and donor CD4 T cells did not cause GvHD damage to target organs. For the first time, we showed that TCF-1 regulates CD4 T cell stemness by regulating CD28 expression, which is required for CD4 stemness. Our data showed that TCF-1 regulates CD4 effector and central memory formation. For the first time, we provide evidence that TCF-1 differentially regulates key chemokine and cytokine receptors critical for CD4 T cell migration and inflammation during alloimmunity. Our transcriptomic data uncovered that TCF-1 regulates critical pathways during normal state and alloimmunity. Knowledge acquired from these discoveries will enable us to develop a target-specific approach for treating CD4 T cell-mediated diseases.
- Subjects
CHEMOKINE receptors; CD4 antigen; GRAFT versus host disease; ALLOIMMUNITY; CELL physiology; BRAIN death; CYTOKINE receptors
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 5, p4326
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24054326