Lack of T cells in Act1-deficient mice results in elevated IgM-specific autoantibodies but reduced lupus-like disease.

European Journal of Immunology
Angela C JohnsonTrine N Jørgensen

Abstract

Act1 is a negative regulator of B-cell activation factor of the TNF family (BAFF) and CD40L-induced signaling. BALB/C mice lacking Act1 develop systemic autoimmunity resembling systemic lupus erythematosus (SLE) and Sjögren's syndrome (SjS). SLE and SjS are characterized by anti-nuclear IgG autoantibody (ANA-IgG) production and inflammation of peripheral tissues. As autoantibody production can occur in a T-cell dependent or T-cell independent manner, we investigated the role of T-cell help during Act1-mediated autoimmunity. Act1-deficiency was bred onto C57Bl/6 (B6.Act1(-/-) ) mice and B6.TCRβ(-/-) TCRδ(-/-) Act1(-/-) (TKO) mice were generated. While TCRβ/δ-sufficient B6.Act1(-/-) mice developed splenomegaly and lymphadenopathy, hypergammaglobulinemia, elevated levels of ANA-IgG, and kidney pathology, TKO mice failed to develop any such signs of disease. Neither B6.Act1(-/-) nor TKO mice developed SjS-like disease, suggesting that epigenetic interactions on the BALB/C background are responsible for this phenotype in BALB/C.Act1(-/-) mice. Interestingly, BAFF-driven transitional B-cell abnormalities, previously reported in BALB/C.Act1(-/-) mice, were intact in B6.Act1(-/-) mice and largely independent of T cells. In conclu...Continue Reading

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Citations

Feb 11, 2014·Expert Review of Clinical Immunology·Amy DonateCuong Q Nguyen
Jan 26, 2020·Nutrients·Erin A YamamotoTrine N Jørgensen
Aug 2, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natalia V GiltiayXiaoxia Li
Jan 18, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Yang HuangJuzhen Yan
Jul 18, 2018·Nature Communications·Cun-Jin ZhangXiaoxia Li
Jul 23, 2020·Frontiers in Immunology·Yunzhen GaoJunfeng Zheng

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