The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant.

The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant.
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DOI:
10.1038/s41598-017-11354-2
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发表时间:
2017-09-06
期刊:
影响因子:
4.6
通讯作者:
Anguita J
Anguita J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tomás-Cortázar J;Martín-Ruiz I;Barriales D;Pascual-Itoiz MÁ;de Juan VG;Caro-Maldonado A;Merino N;Marina A;Blanco FJ;Flores JM;Sutherland JD;Barrio R;Rojas A;Martínez-Chantar ML;Carracedo A;Simó C;García-Cañas V;Abecia L;Lavín JL;Aransay AM;Rodríguez H;Anguita J

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Salp 15是硬蜱的唾液蛋白,抑制幼稚CD 4 T细胞的活化。用Salp 15治疗导致早期信号传导事件的抑制和自分泌生长因子白细胞介素-2的产生。然而,在Salp 15存在下活化的CD 4 T细胞的命运或其长期影响尚不清楚。我们现在表明Salp 15与CD 4的结合是持久的,并诱导持久的免疫调节作用。Salp 15的活性导致持续减少的交叉抗原抗体产生,即使在用该蛋白质治疗中断后。在转录方面,唾液蛋白引起急性效应,包括已知的激活标记物,如IL 2或Cd 44,并随时间推移而消退。Salp 15产生的长期效应不涉及诱导无反应性特征,也不涉及增加调节性T细胞的群体。类似地,用Salp 15处理不会导致B细胞无反应性或产生骨髓抑制细胞。然而,Salp 15诱导调节性T细胞中胞外酶CD 73的表达增加和腺苷的产生增加。我们的研究提供了Salp 15的免疫调节活性的深刻表征,并表明其长期作用是由于CD 73的特异性调节。
Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein. Transcriptionally, the salivary protein provokes an acute effect that includes known activation markers, such as Il2 or Cd44, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with Salp15 does not result in B cell anergy or the generation of myeloid suppressor cells. However, Salp15 induces the increased expression of the ectoenzyme, CD73, in regulatory T cells and increased production of adenosine. Our study provides a profound characterization of the immunomodulatory activity of Salp15 and suggests that its long-term effects are due to the specific regulation of CD73.
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