A unique hybrid renal mononuclear phagocyte activation phenotype in murine systemic lupus erythematosus nephritis.
A unique hybrid renal mononuclear phagocyte activation phenotype in murine systemic lupus erythematosus nephritis.
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DOI：
10.4049/jimmunol.1003010
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发表时间：
2011-04-15
期刊：
影响因子：
--
通讯作者：
Davidson A
中科院分区：
文献类型：
--
作者：
Bethunaickan R;Berthier CC;Ramanujam M;Sahu R;Zhang W;Sun Y;Bottinger EP;Ivashkiv L;Kretzler M;Davidson A
单个核细胞浸润肾脏与SLE预后不良相关肾巨噬细胞/树突状细胞特征与NZB/W小鼠中肾炎的发作相关，并且免疫调节疗法可以逆转该特征和相关的肾损伤，尽管正在进行免疫复合物沉积。在肾炎NZB/W小鼠中，肾F4/80 hi/CD 11 cint巨噬细胞位于整个肾小球，而F4/80 lo/CD 11 chi树突状细胞聚集在血管周围淋巴聚集体中。我们发现F4/80 hi/CD 11 cint肾巨噬细胞具有Gr 1 lo/Ly 6Clo/VLA 4lo/MHCIIhi/CD 43 lo/CD 62 Llo表型，与炎症巨噬细胞不同。在肾炎发作时，F4/80 hi/CD 11 cint细胞上调细胞表面CD 11b，获得组织蛋白酶和MMP活性，并积累大量的自噬空泡;这些变化在诱导缓解后逆转。外周血Gr 1 lo单核细胞的乳胶珠标记表明，这些是F4/80 hi/CD 11 cint巨噬细胞的来源。CD 11 chi/MHCIIlo树突状细胞仅在蛋白尿发作后在肾脏中发现，迅速更新，并在缓解诱导后迅速消失。F4/80 hi/CD 11 cint群体的基因表达谱显示肾炎发作时促炎、调节和组织修复/降解相关基因的表达增加，其随着缓解诱导而逆转。我们的研究结果表明，单核巨噬细胞异常激活有助于狼疮肾炎的组织损伤，介导局部炎症和过度的组织重塑。
Renal infiltration with mononuclear cells is associated with poor prognosis in SLE. A renal macrophage/dendritic cell signature is associated with onset of nephritis in NZB/W mice and immune modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. In nephritic NZB/W mice renal F4/80hi/CD11cint macrophages are located throughout the interstitium whereas F4/80lo/CD11chi dendritic cells accumulate in perivascular lymphoid aggregates. We show here that F4/80hi/CD11cint renal macrophages have a Gr1lo/Ly6Clo/VLA4lo/MHCIIhi/CD43lo/CD62Llo phenotype, different to that described for inflammatory macrophages. At nephritis onset F4/80hi/CD11cint cells upregulate cell surface CD11b, acquire cathepsin and MMP activity and accumulate large numbers of autophagocytic vacuoles; these changes reverse after induction of remission. Latex bead labeling of peripheral blood Gr1lo monocytes indicates that these are the source of F4/80hi/CD11cint macrophages. CD11chi/MHCIIlo dendritic cells are found in the kidneys only after proteinuria onset, turnover rapidly, and disappear rapidly after remission induction. Gene expression profiling of the F4/80hi/CD11cint population displays increased expression of pro-inflammatory, regulatory and tissue repair/degradation associated genes at nephritis onset that reverses with remission induction. Our findings suggest that mononuclear phagocytes with an aberrant activation profile contribute to tissue damage in lupus nephritis by mediating both local inflammation and excessive tissue remodeling.
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DOI：
10.1084/jem.179.1.305
发表时间：
1994-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ishida H;Muchamuel T;Sakaguchi S;Andrade S;Menon S;Howard M
通讯作者：
Howard M
影响因子：
27.4
作者：
Corr M;Boyle DL;Ronacher L;Flores N;Firestein GS
通讯作者：
Firestein GS
影响因子：
20.3
作者：
Mancino, Alessandra;Schioppa, Tiziana;Sica, Antonio
通讯作者：
Sica, Antonio
影响因子：
64.8
作者：
Bouchon, A;Facchetti, F;Colonna, M
通讯作者：
Colonna, M
影响因子：
8.3
作者：
Knight, Sarah F.;Quigley, Jeffrey E.;Imig, John D.
通讯作者：
Imig, John D.