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Nitric oxide controls an inflammatory-like Ly6C(hi)PDCA1+ DC subset that regulates Th1 immune responses.


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-? 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.

SUBMITTER: Giordano D 

PROVIDER: S-EPMC3040463 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Nitric oxide controls an inflammatory-like Ly6C(hi)PDCA1+ DC subset that regulates Th1 immune responses.

Giordano Daniela D   Li Chang C   Suthar Mehul S MS   Draves Kevin E KE   Ma Daphne Y DY   Gale Michael M   Clark Edward A EA  

Journal of leukocyte biology 20101222 3


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)PD  ...[more]

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