Inflammatory monocytes and Fcγ receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice
Inflammatory monocytes and Fcγ receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice
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DOI：
10.1073/pnas.1301001110
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发表时间：
2013-06-25
影响因子：
11.1
通讯作者：
Nimmerjahn, Falk
中科院分区：
文献类型：
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作者：
Seeling, Michaela;Hillenhoff, Ulrike;Nimmerjahn, Falk
破骨细胞对骨组织的破坏是炎性关节炎的严重病理表型，并导致关节疼痛和骨畸形。先前的研究已经确定了细胞因子包括TNF α和受体-配体相互作用的基本作用，例如核因子-κ B的受体活化剂-核因子-κ B配体相互作用的受体活化剂在关节炎症期间对破骨细胞形成的作用。此外，自身抗体通过触发细胞片段可结晶（Fc）γ受体（Fc γ R），导致促炎细胞因子和趋化因子的释放，从而促进先天免疫效应细胞的募集和激活，从而促进炎性关节炎中的关节炎症。相反，很少有人知道的表达模式和不同的Fc γ R在破骨细胞分化的功能。这将允许破骨细胞直接与自身抗体免疫复合物相互作用，而不是通过免疫复合物与其他表达Fc γ R的先天免疫细胞结合后释放的促炎细胞因子间接影响。为了解决这个问题，我们研究了Fc γ R的表达和功能的破骨细胞在稳态和急性关节炎模型中的炎性关节炎。我们的研究结果表明，破骨细胞生成直接受IgG自身抗体结合的影响，以选择激活未成熟破骨细胞上的Fc γ R，从而增强破骨细胞的生成，并最终导致骨破坏。
Destruction of bone tissue by osteoclasts represents a severe pathological phenotype during inflammatory arthritis and results in joint pain and bone malformations. Previous studies have established the essential role of cytokines including TNF alpha and receptor-ligand interactions, such as the receptor activator of nuclear factor-kappa B-receptor activator of nuclear factor-kappa B ligand interaction for osteoclast formation during joint inflammation. Moreover, autoantibodies contribute to joint inflammation in inflammatory arthritis by triggering cellular fragment crystallizable (Fc)gamma receptors (Fc gamma R), resulting in the release of proinflammatory cytokines and chemokines essential for recruitment and activation of innate immune effector cells. In contrast, little is known about the expression pattern and function of different Fc gamma Rs during osteoclast differentiation. This would allow osteoclasts to directly interact with autoantibody immune complexes, rather than being influenced indirectly via proinflammatory cytokines released upon immune complex binding to other Fc gamma R-expressing innate immune cells. To address this question, we studied Fc gamma R expression and function on osteoclasts during the steady state and during acute joint inflammation in a model of inflammatory arthritis. Our results suggest that osteoclastogenesis is directly influenced by IgG autoantibody binding to select activating Fc gamma Rs on immature osteoclasts, resulting in enhanced osteoclast generation and, ultimately, bone destruction.