Overall, the paradoxical enhancement of TGF-β signaling observed in LDS patients with monoallelic LOF variants in TGFBR1 or TGFBR2 makes it difficult to compare observations in humans with data available in mice, where complete ablation of Tgfbr1 or Tgfbr2 in T cells causes a rapidly fatal autoimmune disease characterized by lymphoproliferation, increased T cell activation and cytotoxic differentiation, and drastic Treg cells decrease in the periphery (Table 2) (46–49). The gene discussed is TGFBR2; the disease is autoimmune disease.