A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis.
A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis.
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DOI：
10.1038/srep37789
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发表时间：
2016-11-24
影响因子：
4.6
通讯作者：
Donnelly S
中科院分区：
文献类型：
--
作者：
Lund ME;Greer J;Dixit A;Alvarado R;McCauley-Winter P;To J;Tanaka A;Hutchinson AT;Robinson MW;Simpson AM;O'Brien BA;Dalton JP;Donnelly S
蠕虫寄生虫分泌的分子，有效地调节其宿主的免疫反应，因此，具有治疗免疫介导的人类疾病的潜力。FhHDM-1，一种由寄生虫肝片吸虫分泌的68-mer肽，在两种不同的自身免疫小鼠模型中改善疾病，1型糖尿病和复发-缓解型免疫介导的脱髓鞘。出乎意料的是，FhHDM-1处理不影响自身抗原特异性T细胞的增殖或其细胞因子的产生。然而，在这两种情况下，临床症状的减轻与靶器官（胰岛和脑组织）中免疫细胞浸润的缺乏有关。此外，在肠胃外给药后，FhHDM-1肽与巨噬细胞相互作用并降低其分泌促炎细胞因子如TNF和IL-6的能力。我们提出这种先天促炎免疫反应的抑制，这是在这两种疾病中启动自身免疫的核心，防止了自身反应性淋巴细胞从外周到自身免疫部位的运输（而不是直接调节其功能本身），从而防止了组织破坏。FhHDM-I调节巨噬细胞功能的能力，结合其在多种模型中预防疾病的功效，表明FhHDM-I具有相当大的潜力作为自身免疫性疾病的治疗。
Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases.
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来自蠕虫筋膜的分泌蛋白抑制自动反应性T细胞反应的启动，并防止NOD小鼠中的糖尿病。
影响因子：
3.7
作者：
Lund ME;O'Brien BA;Hutchinson AT;Robinson MW;Simpson AM;Dalton JP;Donnelly S
通讯作者：
Donnelly S
影响因子：
5.4
作者：
Dungan, Lara S.;McGuinness, Niamh C.;Mills, Kingston H. G.
通讯作者：
Mills, Kingston H. G.
影响因子：
4.4
作者：
Kruglov, Andrey A.;Lampropoulou, Vicky;Nedospasov, Sergei A.
通讯作者：
Nedospasov, Sergei A.
影响因子：
4.7
作者：
Bilbo, Staci D.;Wray, Gregory A.;Parker, William
通讯作者：
Parker, William
影响因子：
64.8
作者：
HUTCHINGS, P;ROSEN, H;COOKE, A
通讯作者：
COOKE, A