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Nitric oxide controls an inflammatory-like Ly6C(hi)PDCA1+ DC subset that regulates Th1 immune responses.
Title | Nitric oxide controls an inflammatory-like Ly6C(hi)PDCA1+ DC subset that regulates Th1 immune responses. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Giordano, D, Li, C, Suthar, MS, Draves, KE, Ma, DY, Gale, M, Clark, EA |
Journal | J Leukoc Biol |
Volume | 89 |
Issue | 3 |
Pagination | 443-55 |
Date Published | 2011 Mar |
ISSN | 1938-3673 |
Keywords | Animals, Antigens, CD86, Antigens, Ly, Antigens, Surface, Apoptosis Regulatory Proteins, Biological Markers, CD4-Positive T-Lymphocytes, Cell Proliferation, Cell Survival, Cells, Cultured, Cytokines, Dendritic Cells, Down-Regulation, Epitopes, Immunity, Inflammation, Inflammation Mediators, Interferon-gamma, Mice, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide, Nitric Oxide Synthase Type II, Programmed Cell Death 1 Receptor, Th1 Cells, Toll-Like Receptors, Up-Regulation, West Nile Fever, West Nile virus |
Abstract | Using NOS2 KO mice, we investigated the hypothesis that NO modulation of BM-DC contributes to the NO-mediated control of Th1 immune responses. BM-DCs from NOS2 KO mice, compared with WT BM-DCs, have enhanced survival and responsiveness to TLR agonists, develop more Ly6C(hi)PDCA1(+) DCs that resemble inflammatory DCs and produce high levels of inflammatory cytokines. Also, compared with WT-infected mice, NOS2 KO mice infected with WNV showed enhanced expansion of a similar inflammatory Ly6C(hi)PDCA1(+) DC subset. Furthermore, in contrast to WT DCs, OVA-loaded NOS2 KO BM-DCs promoted increased IFN-γ production by OTII CD4(+) T cells in vitro and when adoptively transferred in vivo. The addition of a NO donor to NOS2 KO BM-DCs prior to OTII T cells priming in vivo was sufficient to revert Th1 immune responses to levels induced by WT BM-DCs. Thus, autocrine NO effects on maturation of inflammatory DCs and on DC programming of T cells may contribute to the protective role of NO in autoimmune diseases and infections. Regulating NO levels may be a useful tool to shape beneficial immune responses for DC-based immunotherapy. |
DOI | 10.1189/jlb.0610329 |
Alternate Journal | J. Leukoc. Biol. |
PubMed ID | 21178115 |