Immunobiology of leukocyte activation
TalTech priority area
Research classification (Frascati)
Head of the research group
Research group member
Doctoral students
Keyword
immune regulation
leukocyte activation
RGS16
P2X4
P2X7
Multiple Sclerosis
melanoma
eosinophils
Covid19
Overview
The group focuses on the biology of leukocyteactivation and its regulation. The control of leukocyte activation is of paramount importance forhealth, both at the steady state and during theimmune response.We have selected two families of regulators ofwhich the immune regulatory functions remainpoorly understood, the RGS (Regulator of Gprotein Signalling; main target RGS16) and thepurinergic receptors (P2X main targets p2x4and p2x7). We studied control mechanisms ofleukocyte activation mediated by these genes inthe context of two pathologies: multiple sclerosisand melanoma.We also followed comparative approaches tounderstand the importance of these genes in thecontext of the evolution of the immune system. We showed that P2X7 receptor resulted fromthe fusion of a P2X4 similar gene with an exonencoding a ballast domain.We also showed in RGS16 KO mice that theexpression of RGS16 by recipient mice inhibitedthe development of grafted melanoma in vivo.[Teras et al 2018 a]. However, this mechanismwas not required for the antitumoral effect of theapoptin protein (ORF3) of the circovirus PCV2,which was based on the induction of apoptosis[Teras et al 2018 b]. In collaboration with PERHwe demonstrated an effective melanoma treatment method (Teras et al 2020; and PhD thesisMarina Teras, collaboration with PERH).
Important results
We published a review where we describe diseases whose physiopathology involves P2X4receptor signaling and summarize that signalingvia P2X4 is highly pH dependent (Kanellopouloset al 2021).
Related projects
Related department
- Schaap, M. J., Bruins, F. M., He, X., Orro, K., Peppelman, M., Van Erp, P. E. J., De Jong, E. M. G. J., Koenen, H. J. P. M., Van Den Bogaard, E. H., Seyger, M. M. B. Skin surface protein detection by transdermal analysis patches in pediatric psoriasis // Skin Pharmacology and Physiology (2021) Vol. 34, Issue 5, p. 271 - 280.
https://doi.org/10.1159/000516110 - Kanellopoulos, J., Almeida-da-Silva, C.L.C, Rüütel Boudinot S., Ojcius D. M. Structural and functional features of the P2X4 receptor : an immunological perspective // Frontiers in immunology (2021) vol. 12, art. 645834, 21 p. : ill.
https://doi.org/10.3389/fimmu.2021.645834 - Teras, J., Teras, M., Pata P., Mägi A., et al. First Eastern European experience of isolated limb infusion for in-transit metastatic melanoma confined to the limb: Is it still an effective treatment option in the modern era? // European journal of surgical oncology (2020) vol. 46, 2, p. 272-276.
https://doi.org/10.1016/j.ejso.2019.10.039 - Teras, M., Viisileht, E., Pahtma-Hall, M., Rump, A., Paalme, V., Pata, P., Pata, I., Langevin, C., Boudinot Ruutel, S. Porcine circovirus type 2 ORF3 protein induces apoptosis in melanoma cells // BMC cancer (2018) Vol. 18, Issue 1, art. 1237, 12 p. : ill.
https://doi.org/10.1186/s12885-018-5090-2 - Teras, M., Rump, A., Paalme, V., Rüütel Boudinot, S. Porcine Circovirus Type 2 ORF3 protein induces apoptoses in melanoma cells // 5th European Congress of Immunology : abstract book. Vienna : ECI, 2018. p. 221.
https://www.eci2018.org/fileadmin/user_upload/documents/ECI_2018_Abstract_Book_web_21082018.pdf - Schaap, M.J., Bruins, F.M., Van Den Brink, N.J.M., Orro, K., Groenewoud, H.M.M., De Jong, E.M.G.J., Van Den Bogaard, E.H., Seyger, M.M.B. Challenges in noninvasive skin biomarker measurements in daily practice : a longitudinal study on skin surface protein detection by the transdermal analysis patch in pediatric psoriasis // Skin Pharmacology and Physiology (2022) Vol. 35, Issue 6, p. 319 - 327.
https://doi.org/10.1159/000527258 - Broman, K. K., Hughes, T., Dossett, L., Sun, J., Kirichenko, D., Carr, M. J., Sharma, A., Bartlett, E. K., Nijhuis, A. A. G., Thompson, J. F., Teras, J., Teras, R. M. et al. Active surveillance of patients who have sentinel node positive melanoma : an international, multi‐institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy trial II (MSLT‐2) // Cancer (2021) vol. 127, 13, p. 2251-2261.
https://doi.org/10.1002/cncr.33483 - Rump, A., Risti, R., Kristal M.-L., Reut, J., Syritski, V., Lõokene, A., Rüütel Boudinot, S. Dual ELISA using SARS-CoV-2 N protein produced in E. coli and CHO cells reveals epitope masking by N-glycosylation // Biochemical and biophysical research communications (2021) vol. 534, p. 457−460.
https://doi.org/10.1016/j.bbrc.2020.11.060 - Broman, K. K., Hughes, T. M., Dossett, L. A., Sun, J., Carr, M. J., Kirichenko, D. A., Sharma, A., Bartlett, E. K., Nijhuis, Amanda AG., Teras, R., Teras, J. et al. Surveillance of sentinel node-positive melanoma patients with reasons for exclusion from MSLT-II: Multi-institutional propensity score matched analysis // Journal of the American College of Surgeons (2021) vol. 232, 4, p. 424-431.
https://doi.org/10.1016/j.jamcollsurg.2020.11.014 - Rump, A., Smolander, O-P., Rüütel-Boudinot, S. et al. Evolutionary origin of the P2X7 C-ter region : capture of an ancient ballast domain by a P2X4-Like gene in ancient jawed vertebrates // Frontiers in immunology (2020) vol. 11, art. 113, 15 p. : ill.
https://doi.org/10.3389/fimmu.2020.00113 - Paalme, V., Speek, M. Simple, inexpensive and RNase-free purification of plasmid DNA by fractional precipitation with isopropanol // BioTechniques (2021) Vol. 71, 3, p. 490−494 : ill.
https://doi.org/10.2144/btn-2021-0018 - Teras, J., Magi, A., Teras, M., Pata, P. et al. Soft tissue cancer management: isolated limb infusion for sarcoma // Visceral medicine (2019) vol. 35, 6, p. 373-379 : ill.
https://doi.org/10.1159/000495888 - Ksenofontov, A.L., Dobrov, E.N., Fedorova, N.V., Paalme, V., Järvekülg, L. et al. Isolated Potato Virus A coat protein possesses unusual properties and forms different short virus-like particles // Journal of biomolecular structure and dynamics (2017) Vol. 36, Issue 7, p. 1-11 : ill.
https://doi.org/10.1080/07391102.2017.1333457 - Paalme, V., Rump, A., Mädo, K., Teras, M., Truumees, B., Aitai, H., Ratas, K., Teras, J., Rüütel Boudinot, S. et al. Human peripheral blood eosinophils express high levels of the purinergic receptor P2X4 // Frontiers in immunology (2019) vol. 10, art. 2074, 15 p. : ill.
https://doi.org/10.3389/fimmu.2019.02074 - Rump, A., Ratas, K., Lepasepp, T. K., Suurväli, J., Smolander, O‐P., Gross‐Paju, K., Toomsoo, T., Kanellopoulos, J., Rüütel Boudinot, S. Sex‐dependent expression levels of VAV1 and P2X7 in PBMC of Multiple Sclerosis patients // Scandinavian journal of immunology (2023) vol. 98, 2, art. e13283, 15 p. : ill.
https://doi.org/10.1111/sji.13283