Table 1.
Summary of transcription factor involvement in GVHD/GVT.
| Factor | Function Impacted | Role | Impact of Loss |
|---|---|---|---|
| Tcf-1 | Cytokine Production, Survival, Proliferation, Chemokines, Gene Expression | Promotes T cell proliferation/survival, controls cytokines/mediators, affects expression of chemokines/receptors, regulates Eomes/T-bet (CD8+ only) | Reduced GVHD, maintained GVT |
| Eomes | Proliferation, Migration, Cytokine Production, Differentiation | Controls T cell migration and proliferation, affects production of cytokines/cytotoxic mediators, impacts Treg fate | Reduced GVHD, reduced GVT |
| T-bet | Migration, Cytokine Production | Controls T cell migration and production of Th1 cytokines | Reduced GVHD, reduced/maintained GVT |
| Notch | Cytokine Production, Proliferation, Differentiation | Controls T cell fate, cytokine production, response to alloantigen, and Treg expansion | Reduced GVHD, maintained GVT |
| Rorγt | Migration, Proliferation, Differentiation | Drives Th17 cell fate, proliferation, and migration | No change/reduced GVHD, maintained GVT |
| Stats | Differentiation, Proliferation, Cytokine Production | Controls Treg/Th subset fate, cytokine production, and proliferation | Reduced (STAT1/3) or enhanced (STAT4/5/6) GVHD, maintained GVT (STAT5/6) |
| Jaks | Differentiation, Proliferation, Cytokine Production | Controls Th1/Th2 polarization, Treg cell fate, proinflammatory cytokines, and T cell proliferation | Reduced GVHD, maintained GVT |
| Bcl6 | Differentiation, Proliferation | Regulates GC formation by Tfh cells and effector CD4+ expansion | Reduced cGVHD |
| Nf-κb | Differentiation, Cytokine Production, Proliferation | Regulates Treg development, cytokines, and T cell expansion | Reduced GVHD, maintained GVT |
| Foxp3 (and Tregs) | Differentiation, Proliferation | Lineage factor for Tregs, stability regulates Treg function | Increased GVHD, maintained GVT |
| c-Rel | Differentiation, Proliferation, Apoptosis, Migration, Cytokine Production | Regulates migration to target organs, formation of Tregs/Th1/Th17, cytokine production, and apoptosis | Reduced GVHD, maintained GVT |
| c-Fos/c-Jun (Ap-1) and c-Myc | Differentiation, Migration, Cytokine Production | May regulate migration, Treg fate, and cytokine production | Reduced GVHD (human studies show possible contradiction) |
| Batf | Differentiation, Proliferation | Controls IL-7/GM-CSF-producing T cells | Reduced GVHD |
| Ezh2 | Proliferation, Differentiation | Regulates long-term proliferation/expansion, promotes differentiation to IFN-γ+ effector fate | Reduced GVHD, maintained GVT |
| Ahr | Proliferation, Migration, Cytokine Production, Differentiation | Regulates pTregs, CD4+ proliferation, CD8+ migration, and proinflammatory cytokine production | Reduced/increased GVHD, maintained GVT |
| Smad3 | Migration, Differentiation, Cytokine Production | Controls Th fate decisions, T cell migration, and proinflammatory cytokines | Reduced allograft rejection, enhanced GVHD |
| Hif1α | Differentiation, Survival | Inhibits Tregs and enhances Th17/Th1 cells | Reduced GVHD, maintained GVT |
| Plzf | Apoptosis, Differentiation | Regulates apoptosis, Th2 fate, and Treg cells | Reduced GVHD, maintained GVT |
| Nfat | Proliferation, Migration, Cytokine Production, Differentiation | Regulates migration, Treg development, cytokine production, and proliferation of T cells | Reduced GVHD, maintained GVT |
| Nrf2 | Differentiation, Migration | Inhibits Helios+ Tregs, controls migration to periphery | Reduced/enhanced GVHD ()?, maintained GVT |
| Fli-1 | Differentiation, Activation | Regulates CD4+ T cell differentiation to Treg/Tfh fates, regulates effector CD4+ T cells | Reduced GVHD, maintained GVT |
| Bhlhe40 | Cytokine Production | Regulates GM-CSF production in CD4+ T cells | Reduced GVHD |