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Tolerogenic nanoparticles targeting B and T lymphocytes delay autoimmune arthritis in K/BxN mice
bioRxiv - Immunology Pub Date : 2020-07-31 , DOI: 10.1101/2020.07.02.185140
Amrita Srivastava , Britni M. Arlian , Lijuan Pang , Takashi K. Kishimoto , James C. Paulson

Current treatments for unwanted antibody responses largely rely on immunosuppressive drugs compromising overall immunity. New approaches to achieve antigen-specific tolerance are desirable to avoid unwanted side effects. Several nanoparticle-based approaches designed to tolerize the B or T cell arms of the humoral immune response have shown promise for induction of antigen-specific tolerance, raising the possibility that they could work synergistically if combined. Earlier we showed that Siglec-engaging tolerance-inducing antigenic liposomes (STALs) that display both an antigen (Ag) and glycan ligands of the inhibitory co-receptor CD22 (CD22L) lead to robust antigen-specific B cell tolerance to protein antigens in naive mice. In another approach, administration of free Ag with poly(lactic co-glycolic acid)-rapamycin nanoparticles (PLGA-R) induced robust antigen-specific tolerance through production of regulatory T cells. Here we illustrate that co-administration of STALs together with PLGA-R to naive mice induced more robust tolerance to multiple antigen challenges than either nanoparticle alone. Moreover, in K/BxN mice that develop spontaneous autoimmune arthritis to the self-antigen glucose-6-phosphate-isomerase (GPI), co-delivery of GPI-LP-CD22L and PLGA-R delayed onset of disease, and in some mice prevented the disease indefinitely. The results show synergy between B cell-tolerizing STALs and T cell-tolerizing PLGA-R and the potential to induce tolerance in early stage autoimmune disease.

中文翻译:

靶向B和T淋巴细胞的致耐受性纳米颗粒延缓了K / BxN小鼠的自身免疫性关节炎

当前用于有害抗体应答的治疗很大程度上依赖于免疫抑制剂,损害了整体免疫力。需要新的方法来达到抗原特异性的耐受性,以避免不必要的副作用。设计用于耐受体液免疫反应的B或T细胞臂的几种基于纳米颗粒的方法已显示出诱导抗原特异性耐受的希望,从而提高了它们联合使用可协同工作的可能性。较早前,我们显示了同时显示抑制性共受体CD22(CD22L)的抗原(Ag)和聚糖配体的Siglec诱导耐受性的抗原脂质体(STAL)导致对幼稚的蛋白抗原的强大的抗原特异性B细胞耐受性老鼠。在另一种方法中 游离Ag与聚乳酸乙醇酸雷帕霉素纳米粒(PLGA-R)的联合给药可通过产生调节性T细胞来产生强大的抗原特异性耐受性。在这里,我们说明了STALs与PLGA-R共同施用给幼稚小鼠比单独使用任何一种纳米颗粒诱导的对多种抗原攻击的耐受性更高。此外,在对自身抗原6-磷酸葡萄糖异构酶(GPI)产生自发性自身免疫性关节炎的K / BxN小鼠中,GPI-LP-CD22L和PLGA-R的共同递送延迟了疾病的发作,并且在某些小鼠中无限期预防了这种疾病。结果表明,耐受B细胞的STAL和耐受T细胞的PLGA-R之间具有协同作用,并且具有在早期自身免疫性疾病中诱导耐受的潜力。在这里,我们说明了STALs与PLGA-R共同施用给幼稚小鼠比单独使用任何一种纳米颗粒诱导的对多种抗原攻击的耐受性更高。此外,在对自身抗原6-磷酸葡萄糖异构酶(GPI)产生自发性自身免疫性关节炎的K / BxN小鼠中,GPI-LP-CD22L和PLGA-R的共同递送延迟了疾病的发作,并且在某些小鼠中无限期预防了这种疾病。结果显示耐受B细胞的STAL和耐受T细胞的PLGA-R之间的协同作用以及在早期自身免疫疾病中诱导耐受的潜力。在这里,我们说明了STALs与PLGA-R共同施用给幼稚小鼠比单独使用任何一种纳米颗粒诱导的对多种抗原攻击的耐受性更高。此外,在对自身抗原6-磷酸葡萄糖异构酶(GPI)产生自发性自身免疫性关节炎的K / BxN小鼠中,GPI-LP-CD22L和PLGA-R的共同递送延迟了疾病的发作,并且在某些小鼠中无限期预防了这种疾病。结果显示耐受B细胞的STAL和耐受T细胞的PLGA-R之间的协同作用以及在早期自身免疫疾病中诱导耐受的潜力。在K / BxN小鼠中,自发性自身免疫性关节炎发展为自身抗原-6-磷酸葡萄糖异构酶(GPI),GPI-LP-CD22L和PLGA-R的共同递送延缓了疾病的发作,在某些小鼠中,它阻止了无限期地疾病。结果显示耐受B细胞的STAL和耐受T细胞的PLGA-R之间的协同作用以及在早期自身免疫疾病中诱导耐受的潜力。在K / BxN小鼠中,自发性自身免疫性关节炎发展为自身抗原-6-磷酸葡萄糖异构酶(GPI),GPI-LP-CD22L和PLGA-R的共同递送延缓了疾病的发作,在某些小鼠中,它阻止了无限期地疾病。结果显示耐受B细胞的STAL和耐受T细胞的PLGA-R之间的协同作用以及在早期自身免疫疾病中诱导耐受的潜力。
更新日期:2020-08-01
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