Abstract
Patients with systemic lupus erythematosus have elevated IFN-α production. Furthermore, sera IFN-α levels correlate with disease activity. We have focused our attention on whether this phenotype is also seen in the New Zealand Black (NZB) mice and simultaneously addressed the underlying mechanisms. Specifically, we analyzed: 1) levels of sera IFN-α after type A CpG ODN 2216 injection in autoimmunity-prone NZB and control mice, and 2) levels of IFN-α synthesized by IFN-α-producing dendritic cells (IPDCs) using highly enriched populations of CD11c+B220+ IPDCs derived from NZB and control mice; IPDCs are divided into two subpopulations (CD4+CD11c+B220+ and CD4 -CD11c+B220+). Our data demonstrate that NZB mice produced higher levels of sera IFN-α after type A CpG ODN 2216 injection when compared with control mice (p < 0.01). In addition, the cell numbers, frequency, and TLR9 mRNA levels of CD4+ and CD4- IPDC were markedly increased in the bone marrow (BM) of NZB mice. Upon in vitro stimulation with TLR9 ligand-CpG ODN 2216, higher levels of IFN-α were synthesized by IPDCs from the BM of NZB. The major contributor of IFN-α was the CD4-CD11c+B220+ IPDC subpopulation. Furthermore, NZB BM IPDCs manifest impaired expression of homing chemokine CCR7 and CD62L, and IL-12 production. These data on the functional characteristics of the IPDC lineages explain in part the mechanism of hyper-IFN-α production and help clarify the mechanism for the expansion of NZB BM IPDCs.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5283-5289 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 173 |
| Issue number | 8 |
| State | Published - Oct 15 2004 |
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- Immunology
Cite this
Expansion of bone marrow IFN-α-producing dendritic cells in New Zealand Black (NZB) mice : High level expression of TLR9 and secretion of IFN-α in NZB bone marrow. / Lian, Zhe Xiong; Kikuchi, Kentaro; Yang, Guo Xiang; Ansari, Aftab A.; Ikehara, Susumu; Gershwin, M. Eric.
In: Journal of Immunology, Vol. 173, No. 8, 15.10.2004, p. 5283-5289.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expansion of bone marrow IFN-α-producing dendritic cells in New Zealand Black (NZB) mice
T2 - High level expression of TLR9 and secretion of IFN-α in NZB bone marrow
AU - Lian, Zhe Xiong
AU - Kikuchi, Kentaro
AU - Yang, Guo Xiang
AU - Ansari, Aftab A.
AU - Ikehara, Susumu
AU - Gershwin, M. Eric
PY - 2004/10/15
Y1 - 2004/10/15
N2 - Patients with systemic lupus erythematosus have elevated IFN-α production. Furthermore, sera IFN-α levels correlate with disease activity. We have focused our attention on whether this phenotype is also seen in the New Zealand Black (NZB) mice and simultaneously addressed the underlying mechanisms. Specifically, we analyzed: 1) levels of sera IFN-α after type A CpG ODN 2216 injection in autoimmunity-prone NZB and control mice, and 2) levels of IFN-α synthesized by IFN-α-producing dendritic cells (IPDCs) using highly enriched populations of CD11c+B220+ IPDCs derived from NZB and control mice; IPDCs are divided into two subpopulations (CD4+CD11c+B220+ and CD4 -CD11c+B220+). Our data demonstrate that NZB mice produced higher levels of sera IFN-α after type A CpG ODN 2216 injection when compared with control mice (p < 0.01). In addition, the cell numbers, frequency, and TLR9 mRNA levels of CD4+ and CD4- IPDC were markedly increased in the bone marrow (BM) of NZB mice. Upon in vitro stimulation with TLR9 ligand-CpG ODN 2216, higher levels of IFN-α were synthesized by IPDCs from the BM of NZB. The major contributor of IFN-α was the CD4-CD11c+B220+ IPDC subpopulation. Furthermore, NZB BM IPDCs manifest impaired expression of homing chemokine CCR7 and CD62L, and IL-12 production. These data on the functional characteristics of the IPDC lineages explain in part the mechanism of hyper-IFN-α production and help clarify the mechanism for the expansion of NZB BM IPDCs.
AB - Patients with systemic lupus erythematosus have elevated IFN-α production. Furthermore, sera IFN-α levels correlate with disease activity. We have focused our attention on whether this phenotype is also seen in the New Zealand Black (NZB) mice and simultaneously addressed the underlying mechanisms. Specifically, we analyzed: 1) levels of sera IFN-α after type A CpG ODN 2216 injection in autoimmunity-prone NZB and control mice, and 2) levels of IFN-α synthesized by IFN-α-producing dendritic cells (IPDCs) using highly enriched populations of CD11c+B220+ IPDCs derived from NZB and control mice; IPDCs are divided into two subpopulations (CD4+CD11c+B220+ and CD4 -CD11c+B220+). Our data demonstrate that NZB mice produced higher levels of sera IFN-α after type A CpG ODN 2216 injection when compared with control mice (p < 0.01). In addition, the cell numbers, frequency, and TLR9 mRNA levels of CD4+ and CD4- IPDC were markedly increased in the bone marrow (BM) of NZB mice. Upon in vitro stimulation with TLR9 ligand-CpG ODN 2216, higher levels of IFN-α were synthesized by IPDCs from the BM of NZB. The major contributor of IFN-α was the CD4-CD11c+B220+ IPDC subpopulation. Furthermore, NZB BM IPDCs manifest impaired expression of homing chemokine CCR7 and CD62L, and IL-12 production. These data on the functional characteristics of the IPDC lineages explain in part the mechanism of hyper-IFN-α production and help clarify the mechanism for the expansion of NZB BM IPDCs.
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M3 - Article
C2 - 15470074
AN - SCOPUS:6344227970
VL - 173
SP - 5283
EP - 5289
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 8
ER -