| First Author | Cho MJ | Year | 2023 |
| Journal | Exp Mol Med | Volume | 55 |
| Issue | 5 | Pages | 1033-1045 |
| PubMed ID | 37121980 | Mgi Jnum | J:353826 |
| Mgi Id | MGI:7486911 | Doi | 10.1038/s12276-023-00995-1 |
| Citation | Cho MJ, et al. (2023) Steady-state memory-phenotype conventional CD4(+) T cells exacerbate autoimmune neuroinflammation in a bystander manner via the Bhlhe40/GM-CSF axis. Exp Mol Med 55(5):1033-1045 |
| abstractText | Memory-phenotype (MP) CD4(+) T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4(+) T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4(+) T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure. Distinct subpopulations of MP CD4(+) T cells were specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells exerted TCR-independent bystander effector functions similar to innate lymphoid cells. In particular, CCR6(high) subpopulation of MP CD4(+) T cells were major responders to IL-23 and IL-1beta without MOG(35-55) antigen reactivity, which gave them pathogenic Th17 characteristics and allowed them to contribute to autoimmune encephalomyelitis. We identified that Bhlhe40 in CCR6(high) MP CD4(+) T cells as a key regulator of GM-CSF expression through IL-23 and IL-1beta signaling, contributing to central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal the clearly distinct effector-like heterogeneity of MP CD4(+) T cells in the steady state and indicate that CCR6(high) MP CD4(+) T cells exacerbate autoimmune neuroinflammation via the Bhlhe40/GM-CSF axis in a bystander manner. |
