Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rheumatoid arthritis.
Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rheumatoid arthritis.
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免疫调节基质结合纳米微囊可缓解由Pristane诱导的急慢性类风湿性关节炎。
DOI：
10.1038/s41536-022-00208-9
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发表时间：
2022-02-02
影响因子：
7.2
通讯作者：
Badylak SF
中科院分区：
文献类型：
--
作者：
Crum RJ;Hall K;Molina CP;Hussey GS;Graham E;Li H;Badylak SF
类风湿性关节炎（RA）是一种以滑膜关节慢性炎症和破坏为特征的自身免疫性疾病，全球约有750万人受到影响。疾病病理是由促炎与抗炎免疫细胞，特别是巨噬细胞比例的不平衡所驱动的。由细胞外基质（ECM）组成的生物支架材料可以诱导巨噬细胞表型的调节，特别是从M1到M2，从亲抗炎到抗炎的转变。基于ECM的免疫调节作用被认为部分是通过最近发现的嵌入ECM中的基质结合纳米囊泡（MBV）介导的。分离的MBV通过静脉注射（i.v.）或关节周围注射（p.a.）给普利斯坦诱导的关节炎（PIA）大鼠。MBV给药的结果与临床护理标准甲氨蝶呤（MTX）腹腔注射（i.p）给药的结果进行了比较。与患病动物相比，i.p MTX、i.v MBV和p.a MBV均能降低急性和慢性前列腺素性关节炎的关节炎评分，减轻滑膜炎症，减少不良关节重塑，降低滑膜和脾脏M1 / M2巨噬细胞的比例（p < 0.05）。p.a.和静脉注射MBV均可降低RA和PIA急性和慢性期血清标志物CXCL10和MCP-3的浓度（p < 0.05）。流式细胞术显示存在系统性CD43hi/His48lo/CD206+，免疫调节单核细胞群独特于p.a.和静脉注射MBV治疗与疾病消退相关。结果表明，MBV治疗急性和慢性前列腺素诱导关节炎的疗效与MTX相同，而且，这种效果与局部滑膜巨噬细胞和全身髓细胞群的调节有关。
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and destruction of synovial joints affecting ~7.5 million people worldwide. Disease pathology is driven by an imbalance in the ratio of pro-inflammatory vs. anti-inflammatory immune cells, especially macrophages. Modulation of macrophage phenotype, specifically an M1 to M2, pro- to anti-inflammatory transition, can be induced by biologic scaffold materials composed of extracellular matrix (ECM). The ECM-based immunomodulatory effect is thought to be mediated in part through recently identified matrix-bound nanovesicles (MBV) embedded within ECM. Isolated MBV was delivered via intravenous (i.v.) or peri-articular (p.a.) injection to rats with pristane-induced arthritis (PIA). The results of MBV administration were compared to intraperitoneal (i.p.) administration of methotrexate (MTX), the clinical standard of care. Relative to the diseased animals, i.p. MTX, i.v. MBV, and p.a. MBV reduced arthritis scores in both acute and chronic pristane-induced arthritis, decreased synovial inflammation, decreased adverse joint remodeling, and reduced the ratio of synovial and splenic M1 to M2 macrophages (p < 0.05). Both p.a. and i.v. MBV reduced the serum concentration of RA and PIA biomarkers CXCL10 and MCP-3 in the acute and chronic phases of disease (p < 0.05). Flow-cytometry revealed the presence of a systemic CD43hi/His48lo/CD206+, immunoregulatory monocyte population unique to p.a. and i.v. MBV treatment associated with disease resolution. The results show that the therapeutic efficacy of MBV is equal to that of MTX for the management of acute and chronic pristane-induced arthritis and, further, this effect is associated with modulation of local synovial macrophages and systemic myeloid populations.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
DOI：
10.1073/pnas.0905851106
发表时间：
2010-02-23
影响因子：
11.1
作者：
Agrawal, Vineet;Johnson, Scott A.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
4.9
作者：
Andreas, Kristin;Luebke, Carsten;Sittinger, Michael
通讯作者：
Sittinger, Michael
影响因子：
14
作者：
Brown, Bryan N.;Valentin, Jolene E.;Stewart-Akers, Ann M.;McCabe, George P.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
7.2
作者：
Dziki, Jenna;Badylak, Stephen;Rubin, J. Peter
通讯作者：
Rubin, J. Peter