CD8+ T cell loss induces autoinflammation in inborn errors of cell death - PubMed
14 hours ago
- #autoinflammation
- #RIPK1
- #CD8+ T cells
- CD8+ T cell loss induces autoinflammation in inborn errors of cell death (IECD).
- Patients with compound heterozygous RIPK1 variants K377E/R390G exhibit autoinflammatory manifestations due to suppressed NF-κB signaling and activated RIPK1-mediated cell death.
- CD8+ T cells in patients show excessive RIPK1 activation and cell death, leading to an elevated CD4/CD8 ratio, also observed in other IECD conditions.
- Increased CD8+ T cell death promotes TNF and IFN-γ secretion, activating monocytes/macrophages and triggering proinflammatory cytokine overproduction.
- Blocking TNF and IFN-γ communication between T cells and monocytes/macrophages reduces inflammation and alleviates symptoms in patients.
- Elevated CD4/CD8 ratio and RIPK1 activation in T cells may serve as diagnostic criteria for RIPK1-dependent IECD.
- Combination therapy with TNF/JAK inhibitors could be effective for treating RIPK1-dependent IECD patients.