2024 年 25 巻 p. 50-54
Studies on systemic lupus erythematosus （SLE） model mice and human SLE patients have revealed that Toll-like receptor （TLR） 7 is involved in the onset of SLE. Since systemic autoimmune diseases develop due to enhanced expression of TLR7, we predicted that the TLR7 response is particularly tightly regulated, and we identified molecules associated with TLR7 using liquid chromatography-mass spectrometry. The molecule we identified was a small G protein called Arl8b, which is localized in endosomes and lysosomes. Arl8b is involved in the movement and fusion of endosomes and lysosomes, and regulates type 1 interferon production induced by TLR7 stimulation. Since the constitutive type 1 interferon production induced by TLR7 stimulation may be closely linked to the onset of SLE, we created BXSB.Yaa Arl8b-deficient mice by crossing BXSB.Yaa mice, which develop SLE in a TLR7-dependent manner, with Arl8b-deficient mice. The BXSB.Yaa Arl8b-deficient mice did not develop SLE at all. Furthermore, in a model of SLE induction by pristane administration, in which TLR7-dependent type 1 interferon causes SLE, the disease induction was significantly suppressed in Arl8b-deficient mice. Our research to date has revealed that Arl8b is involved in the onset of SLE through TLR7-dependent and TLR7-independent pathways. Research on how Arl8b is involved in the pathogenesis of SLE is expected to make significant progress in the future.
