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.
Dietlin
Therese A
TA
Department of Neurology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Cua
Daniel J
DJ
Burke
Kathleen A
KA
Lund
Brett T
BT
van der Veen
Roel C
RC
D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D000950:Antigens, Ly; D015551:Autoimmunity; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D019650:Hematopoietic Stem Cell Mobilization; D006358:Hot Temperature; D007108:Immune Tolerance; D007114:Immunization; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine; D013154:Spleen / Q000473:pathology; D013481:Superoxides / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000942:Antigens, Bacterial; D000950:Antigens, Ly; C503133:Gr-1 protein, mouse; D053759:Interleukin-23; C480309:Ly6G antigen, mouse; C111390:OVA 323-339; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D019707:Receptors, Chemokine; D013481:Superoxides; D009569:Nitric Oxide; D010047:Ovalbumin