Colony-stimulating factor-1-dependent macrophages are responsible for IVIG protection in antibody-induced autoimmune disease

被引:259
作者
Bruhns, P
Samuelsson, A
Pollard, JW
Ravetch, JV
机构
[1] Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA
[2] Albert Einstein Coll Med, Dept Dev & Mol Biol & Obstet & Gynecol & Womens H, Bronx, NY 10461 USA
关键词
D O I
10.1016/S1074-7613(03)00080-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The ability of IVIG to induce expression of FcgammaRIIB and thereby prevent antibody-induced inflammation has been used as a probe to dissect the effector cell components in the KRNxNOD (K/BxN) arthritis model. IVIG protection resulted from the induction of FcgammaRIIB on infiltrating macrophages but not neutrophils, indicating a critical role for macrophage activation in this disease model. Disease induction but not IVIG protection was observed in CSF-1-deficient mice (op/op) in K/BxN arthritis, thus defining different macrophage subsets in these processes. These results suggest a two-step model for IVIG protection in which CSF-1-dependent macrophages act as innate "sensors" for the Fc fragment of IVIG, leading to the induction of FcgammaRIIB on CSF-1-independent "effector" macrophages thereby raising the threshold required for FcgammaRIII activation and preventing autoantibody-triggered inflammation.
引用
收藏
页码:573 / 581
页数:9
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