Identification of a region in p47phox/NCF1 crucial for phagocytic NADPH oxidase (NOX2) activation.

A point mutation in the mouse Ncf1(m1J) gene decreases production of ROS by the phagocytic NOX2 complex. Three mRNA splice variants are expressed, but only one is expressed as a protein, although at lower levels than the WT NCF1 (also known as p47phox). Our aim was to investigate whether the mutant p47phox, lacking 8 aa, is active, but as a result of its low expression, ROS production is decreased in Ncf1(m1J) mice, or whether the mutant p47phox completely lacks the capability to activate the NOX2 complex.

Hydrogen peroxide as an immunological transmitter regulating autoreactive T cells.

Significance: An unexpected finding, revealed by positional cloning of genetic polymorphisms controlling models for rheumatoid arthritis, exposed a new function of Ncf1 and NADPH oxidase (NOX) 2 controlled oxidative burst.

Recent Advances: A decreased capacity to produce ROS due to a natural polymorphism was found to be the major factor leading to more severe arthritis and increased T cell-dependent autoimmunity.

Critical Issues: In the vein of this finding, we here review a possible new role of ROS in regulating inflammatory cell and autoreactive T cell activity.