ABSTRACT Nitric oxide (NO) has strong immune suppressive capacities, but the regulation of its activity remains ill defined. NO is produced by Gr-1 cells during immune T cell activation. Our results indicate that superoxide (O2‾) is produced simultaneously at short range and reduces NO’s suppressive activity. Superoxide dismutase reverses the inactivation of NO by O2‾. Interestingly, NO and O2‾ are produced by distinct immature monocytic and granulocytic cells, respectively, which are distinguishable by Ly-6G expression. IL-23, required for autoimmune inflammation, is involved in the mobilization of both Gr-1 subsets to different degrees, following exposure to mycobacterial products. From these results, a model emerges of an interactive immune regulatory system, named Greg, consisting of two immature myeloid Gr-1+ subsets from distinct lineages. They are mobilized by innate mechanisms involving IL-23, and produce NO or O2‾ when activated. The degree of NO inactivation by O2‾ determines the intensity of inflammation.
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