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

Abstract

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 “G reg ” subsets, which, upon stimulation by activated T cells, produce immunoregulatory superoxide (O 2 −) and nitric oxide (NO), respectively. The balance between immunosuppressive NO and its antagonist O 2 − regulates T cell expansion, similar to regulation of vasodilation. Reduction of NO levels by O 2 − 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 G reg subsets expressing strong activity. In the spleens of primed IL-23 −/− mice, Ly-6G + cells remained at naïve levels and produced no O 2 −. 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 O 2 − 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 O 2 −- and NO-producing Gr-1 + cells from BM, which may contribute to its widely studied role in (auto)immunity.