Autoimmune disorder phenotypes in Hvcn1-deficient mice

作者：Sasaki Mari; Tojo Akihiro; Okochi Yoshifumi; Miyawaki Nana; Kamimura Daisuke; Yamaguchi Akihito; Murakami Masaaki; Okamura Yasushi^*

来源：Biochemical Journal, 2013, 450(2): 295-301.

DOI：10.1042/BJ20121188

• anti-DNA antibody
• nephritis
• pH regulation
• reactive oxygen species
• T-cell
• voltage-gated proton channel (H-v channel)

H-v channels (voltage-gated proton channels) are expressed in blood cells, microglia and some types of epithelial cells. In neutrophils H-v channels regulate the production of reactive oxygen species through regulation of membrane potential and intracellular pH. H-v channels have also been suggested to play a role in sperm physiology in the human. However, the functions of the H-v channel at the whole-body level are not fully understood. In the present paper we show that Hvcn1 (voltage-gated hydrogen channel 1)-knockout mice show splenomegaly, autoantibodies and nephritis, that are reminiscent of human autoimmune diseases phenotypes. The number of activated T-cells was larger in Hvcn1-deficient mice than in the wild-type mice., Upon viral infection this was remarkably enhanced in Hvcn1-deficient mice. The production of superoxide anion in T-cells upon stimulation with PMA was significantly attenuated in the Hvcn1-deficient mice. These results suggest that H-v channels regulate T-cell homoeostasis in vivo.

• 出版日期2013-3-1