Milk-based nutraceutical for treating autoimmune arthritis via the stimulation of IL-10- and TGF-β-producing CD39+ regulatory T cells.
Milk-based nutraceutical for treating autoimmune arthritis via the stimulation of IL-10- and TGF-β-producing CD39+ regulatory T cells.
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DOI：
10.1371/journal.pone.0117825
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Pascual DW
中科院分区：
文献类型：
--
作者：
Maddaloni M;Kochetkova I;Jun S;Callis G;Thornburg T;Pascual DW
自身免疫性疾病由对自身的耐受性丧失引起，并且由于这些疾病的病因在很大程度上是未知的，对症治疗依赖于抗炎和镇痛剂。可以逆转疾病的致耐受性治疗是优选的，但同样，由于不知道负责的自身抗原（auto-Ags）而经常受阻。因此，刺激调节性T细胞（Tcells）的可行替代方案是诱导旁观者耐受。已显示定殖因子抗原I（CFA/I）引起旁观者免疫并独立于自身Ag加速Ag特异性Treg发育。为了转化为治疗人类自身免疫性疾病，基于食物的乳球菌被工程化以表达CFA/I菌毛，并且喂养关节炎小鼠的乳球菌-CFA/I发酵乳被证明是高度有效的。通过产生TGF-β和IL-10的CD 39 + T细胞产生保护作用，以有效抑制TNF-α产生和中性粒细胞流入关节。因此，这些数据证明了口服营养品治疗关节炎的可行性，并且相对于用沙门氏菌-CFA/I获得的保护效力，针对关节炎的保护效力得到了改善。
Autoimmune diseases arise from the loss of tolerance to self, and because the etiologies of such diseases are largely unknown, symptomatic treatments rely on anti-inflammatory and analgesic agents. Tolerogenic treatments that can reverse disease are preferred, but again, often thwarted by not knowing the responsible auto-antigens (auto-Ags). Hence, a viable alternative to stimulating regulatory T cells (Tregs) is to induce bystander tolerance. Colonization factor antigen I (CFA/I) has been shown to evoke bystander immunity and to hasten Ag-specific Treg development independent of auto-Ag. To translate in treating human autoimmune diseases, the food-based Lactococcus was engineered to express CFA/I fimbriae, and Lactococcus-CFA/I fermented milk fed to arthritic mice proved highly efficacious. Protection occurred via CD39+ Tregs producing TGF-β and IL-10 to potently suppress TNF-α production and neutrophil influx into the joints. Thus, these data demonstrate the feasibility of oral nutraceuticals for treating arthritis, and potency of protection against arthritis was improved relative to that obtained with Salmonella-CFA/I.
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DOI：
10.4049/jimmunol.1302018
发表时间：
2014-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kochetkova I;Thornburg T;Callis G;Holderness K;Maddaloni M;Pascual DW
通讯作者：
Pascual DW
影响因子：
5.4
作者：
Behnsen, Judith;Deriu, Elisa;Raffatellu, Manuela
通讯作者：
Raffatellu, Manuela
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
DOI：
10.1073/pnas.0812843106
发表时间：
2009-06-30
影响因子：
11.1
作者：
Li, Yong-Fu;Poole, Steven;Bullitt, Esther
通讯作者：
Bullitt, Esther
影响因子：
3.2
作者：
SMITH, HR;WILLSHAW, GA;ROWE, B
通讯作者：
ROWE, B