Haploinsufficiency of A20 is strongly implicated in various human autoimmune diseases. The combination of heterozygous A20 ablation with overexpression of anti-apoptotic BclxL specifically in B cells was sufficient to induce a lethal systemic autoimmune pathology, recapitulating many features of human SLE, in mice. Paradoxically, mice with complete B cell-specific knockout of A20 were spared from lethal disease. The reason relies in the induction of a T cell checkpoint counteracting the expansion of strongly hyperreactive B but sparing mildly hyperreactive B cells.
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Haploinsufficiency of A20 is strongly implicated in various human autoimmune diseases. The combination of heterozygous A20 ablation with overexpression of anti-apoptotic BclxL specifically in B cells was sufficient to induce a lethal systemic autoimmune pathology, recapitulating many features of human SLE, in mice. Paradoxically, mice with complete B cell-specific knockout of A20 were spared from lethal disease. The reason relies in the induction of a T cell checkpoint counteracting the expansio...
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