TY - JOUR
T1 - IL-10 deficiency blocks the ability of LPS to regulate expression of tolerance-related molecules on dendritic cells
AU - Zhou, Fang
AU - Ciric, Bogoljub
AU - Li, Hongmei
AU - Yan, Yaping
AU - Li, Ke
AU - Cullimore, Melissa
AU - Lauretti, Elisabetta
AU - Gonnella, Patricia
AU - Zhang, Guang Xian
AU - Rostami, Abdolmohamad
PY - 2012/6
Y1 - 2012/6
N2 - Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays an important role in regulating the local inflammatory immune response, but regulatory mechanisms of this cytokine have not been fully elucidated. Here, we demonstrate that IL-10 deficiency renders LPS treatment ineffective in regulating the expression of CD40, CD80, CD86, B7-H2, and B7-DC on dendritic cells (DCs) and blocks upregulation of IL-27. This inability to respond to LPS was found in both IL-10-/- bone marrow derived and splenic DCs. Compared with wild-type DCs, IL-10-/- DCs expressed similar levels of TLR4 and CD14, but produced less LPS-binding protein. The deficiency in LPS-binding protein production may explain the failure of IL-10-/- DCs to respond normally to LPS. Moreover, lack of IL-10 modulated the proportions of CD11c+CD8+ and CD11c+B220+ DCs, which play an important role in local inflammatory responses and tolerance. IL-10 deficiency also blocked expression of galectin-1, CD205, and CD103, which are necessary for central and peripheral tolerance. While they did not respond to LPS, IL-10-/- DCs produced increased levels of IL-6 and CCL4 after TNF-α treatment. Together, our results demonstrate that IL-10 deficiency affects the immune functions of DCs, which may contribute to the increased severity of autoimmune diseases seen in IL-10-/- mice.
AB - Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays an important role in regulating the local inflammatory immune response, but regulatory mechanisms of this cytokine have not been fully elucidated. Here, we demonstrate that IL-10 deficiency renders LPS treatment ineffective in regulating the expression of CD40, CD80, CD86, B7-H2, and B7-DC on dendritic cells (DCs) and blocks upregulation of IL-27. This inability to respond to LPS was found in both IL-10-/- bone marrow derived and splenic DCs. Compared with wild-type DCs, IL-10-/- DCs expressed similar levels of TLR4 and CD14, but produced less LPS-binding protein. The deficiency in LPS-binding protein production may explain the failure of IL-10-/- DCs to respond normally to LPS. Moreover, lack of IL-10 modulated the proportions of CD11c+CD8+ and CD11c+B220+ DCs, which play an important role in local inflammatory responses and tolerance. IL-10 deficiency also blocked expression of galectin-1, CD205, and CD103, which are necessary for central and peripheral tolerance. While they did not respond to LPS, IL-10-/- DCs produced increased levels of IL-6 and CCL4 after TNF-α treatment. Together, our results demonstrate that IL-10 deficiency affects the immune functions of DCs, which may contribute to the increased severity of autoimmune diseases seen in IL-10-/- mice.
KW - Costimulatory molecule · DCs · IL-10 · TLR4
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U2 - 10.1002/eji.201141733
DO - 10.1002/eji.201141733
M3 - Article
C2 - 22622800
AN - SCOPUS:84862116936
SN - 0014-2980
VL - 42
SP - 1449
EP - 1458
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 6
ER -