RT Journal Article T1 The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant A1 Tomás-Cortázar, Julen A1 Martín-Ruiz, Itziar A1 Barriales, Diego A1 Pascual-Itoiz, Miguel Ángel A1 de Juan, Virginia Gutiérrez A1 Caro-Maldonado, Alfredo A1 Merino, Nekane A1 Marina, Alberto A1 Blanco, Francisco J. A1 Flores Landeira, Juana María A1 Sutherland, James D. A1 Barrio, Rosa A1 Rojas, Adriana A1 Martínez-Chantar, María Luz A1 Carracedo, Arkaitz A1 Simó, Carolina A1 García-Cañas, Virginia A1 Abecia, Leticia A1 Lavín, José Luis A1 Aransay, Ana M. A1 Rodríguez, Héctor A1 Anguita, Juan AB 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 PB Nature Research YR 2017 FD 2017-09-06 LK https://hdl.handle.net/20.500.14352/125909 UL https://hdl.handle.net/20.500.14352/125909 LA eng NO Tomás-Cortázar, J., Martín-Ruiz, I., Barriales, D., Pascual-Itoiz, M. Á., de Juan, V. G., Caro-Maldonado, A., Merino, N., Marina, A., Blanco, F. J., Flores, J. M., Sutherland, J. D., Barrio, R., Rojas, A., Martínez-Chantar, M. L., Carracedo, A., Simó, C., García-Cañas, V., Abecia, L., Lavín, J. L., Aransay, A. M., … Anguita, J. (2017). The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant. Scientific reports, 7(1), 10740. https://doi.org/10.1038/s41598-017-11354-2 NO Author Contributions: Performed the experiments: J.T.C., I.M.M., D.B., M.A.P.I., V.G.J., A.C.M., N.M., A.M., J.M.F., C.S., V.G.C., J.A. Analyzed the data: J.T.C., J.L.L., A.M.A., H.R., J.A. Provided reagents: F.J.B., J.D.S., R.B., A.R., M.L.M.C. Wrote the manuscript: J.T.C., A.C., L.A., H.R., J.A., J.A. designed the study and provided supervision NO Departamento de Educación del Gobierno Vasco NO European Commission NO Departamento Vasco de Industria, Turismo y Comercio NO Departamento de Tecnología e Innovación de Bizkaia y la Red CIBERehd NO Ministerio de Economía, Comercio y Empresa ( España ) DS Docta Complutense RD 21 ene 2026