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

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. Introduction

Bibliographic Details

Main Authors:	Tomás-Cortázar, Julen, Martín-Ruiz, Itziar, Barriales, Diego, Pascual-Itoiz, Miguel Ángel, Gutiérrez de Juan, Virginia, Caro-Maldonado, Alfredo, Merino, Nekane, Marina, Alberto, Blanco, Francisco J., Flores, Juana María, Sutherland, James D., Barrio, Rosa, Rojas, Adriana, Martínez-Chantar, María Luz, Carracedo, Arkaitz, Simó, Carolina, García-Cañas, Virginia, Abecia, Leticia, Lavín, José Luis, Aransay, Ana M., Rodríguez, Héctor, Anguita, Juan
Other Authors:	European Commission
Format:	artículo biblioteca
Language:	English
Published:	Springer Nature 2017
Online Access:	http://hdl.handle.net/10261/194249 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100000781 http://dx.doi.org/10.13039/501100003086
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