Role of IL-23 in mobilization of immunoregulatory nitric oxide- or superoxide-producing Gr-1+ cells from bone marrow.

Spleens of mice injected with heat-killed Mycobacterium tuberculosis increase their Gr-1+ cell content and develop a system of interactive Ly-6G+ and Ly-6G-Gr-1+ populations or "Greg" subsets, which, upon stimulation by activated T cells, produce immunoregulatory superoxide (O2(-)) and nitric oxide (NO), respectively. The balance between immunosuppressive NO and its antagonist O2(-) regulates T cell expansion, similar to regulation of vasodilation. Reduction of NO levels by O2(-) is required for efficient T cell expansion and development of autoimmunity. We studied the source of Gr-1+ cells in bone marrow (BM), where their levels were higher than in spleen, with both Greg subsets expressing strong activity. In the spleens of primed IL-23-/- mice, Ly-6G+ cells remained at naïve levels and produced no O2(-). The complementary Ly-6G(-)Gr-1+ splenocytes and their suppressive activity were partially reduced. Surprisingly, Gr-1+ cell levels in BM of IL-23-/- mice were increased, as were their O2(-) and NO production. Transfer of primed BM cells partially restored regulatory function in the spleen of IL-23-/- recipients. The results suggest that IL-23 is involved in mobilization of O2(-)- and NO-producing Gr-1+ cells from BM, which may contribute to its widely studied role in (auto)immunity.