Tolerogenic Nanoparticles Impacting B and T Lymphocyte Responses Delay Autoimmune Arthritis in K/BxN Mice.
Tolerogenic Nanoparticles Impacting B and T Lymphocyte Responses Delay Autoimmune Arthritis in K/BxN Mice.
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DOI：
10.1021/acschembio.1c00212
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发表时间：
2021-10-15
影响因子：
4
通讯作者：
Paulson JC
中科院分区：
文献类型：
--
作者：
Srivastava A;Arlian BM;Pang L;Kishimoto TK;Paulson JC
目前对不想要的抗体反应的治疗很大程度上依赖于损害整体免疫力的免疫抑制药物。实现抗原特异性耐受性的新方法是可取的，以避免不必要的副作用。几种基于纳米颗粒的方法利用不同的机制来耐受体液免疫反应的B细胞或T细胞臂，已经显示出诱导抗原特异性耐受的希望，这提高了它们联合起来协同工作的可能性。先前我们发现，在naïve小鼠中，siglece接合的耐受性诱导抗原脂体（STALs）同时显示抗原（Ag）和抑制性共受体CD22 （CD22L）的糖聚糖配体，导致对蛋白质抗原具有强大的抗原特异性B细胞耐受性。在另一种方法中，通过产生调节性T细胞，将游离Ag与聚乳酸共乙醇酸-雷帕霉素纳米颗粒（PLGA-R）一起施用，诱导了强大的抗原特异性耐受性。研究表明，与单独给药相比，STALs和PLGA-R共同给药naïve小鼠对多种抗原的耐受性更强。此外，在对自身抗原葡萄糖-6-磷酸异构酶（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，并且在一些小鼠中无限期地预防了疾病。结果显示B细胞耐受性STALs和T细胞耐受性PLGA-R之间的协同作用以及在早期自身免疫性疾病中诱导耐受性的潜力。
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 that utilize different mechanisms 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 naïve 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 naïve 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.
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影响因子：
14.2
作者：
Burks, A. Wesley;Calderon, Moises A.;Akdis, Cezmi A.
通讯作者：
Akdis, Cezmi A.
影响因子：
17.1
作者：
Hunter Z;McCarthy DP;Yap WT;Harp CT;Getts DR;Shea LD;Miller SD
通讯作者：
Miller SD
DOI：
10.1073/pnas.1408686111
发表时间：
2015-01-13
影响因子：
11.1
作者：
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通讯作者：
Kishimoto, Takashi Kei
影响因子：
1.9
作者：
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通讯作者：
Kishnani, Priya S.
影响因子：
7.8
作者：
Kwun J;Bulut P;Kim E;Dar W;Oh B;Ruhil R;Iwakoshi N;Knechtle SJ
通讯作者：
Knechtle SJ