Immunosuppressive evidence of Tityus serrulatus toxins Ts6 and Ts15: insights of a novel K+ channel pattern in T cells

Author(s)

Pucca, Manuela B. ; Bertolini, Thais B. ; Cerni, Felipe A. ; Bordon, Karla C. F. ; Peigneur, Steve ; Tytgat, Jan ; Bonato, Vania L. ; Arantes, Eliane C.

• Document type: Journal article
• Source: IMMUNOLOGY; v. 147, n. 2, p. 11-pg., 2016-02-01.

Abstract

The voltage-gated potassium channel Kv1.3 is a novel target for immunomodulation of autoreactive effector memory T cells, which play a major role in the pathogenesis of autoimmune diseases. In this study, the Ts6 and Ts15 toxins isolated from Tityus serrulatus (Ts) were investigated for their immunosuppressant roles on CD4(+) cell subsets: naive, effector (TEF), central memory (T-CM) and effector memory (T-EM). The electro-physiological assays confirmed that both toxins were able to block Kv1.3 channels. Interestingly, an extended Kv channel screening shows that Ts15 blocks Kv2.1 channels. Ts6 and Ts15 significantly inhibit the proliferation of T-EM cells and interferon-c production; however, Ts15 also inhibits other CD4(+) cell subsets (naive, TEF and T-CM). Based on the Ts15 inhibitory effect of proliferation of all CD4(+) cell subsets, and based on its blocking effect on Kv2.1, we investigated the Kv2.1 expression in T cells. The assays showed that CD4(+) and CD8(+) cells express the Kv2.1 channels mainly extracellularly with T-CM cells expressing the highest number of Kv2.1 channels. We also provide in vivo experimental evidence to the protective effect of Ts6 and Ts15 on delayed-type hypersensitivity reaction. Altogether, this study presents the immunosuppressive behaviour of Ts6 and Ts15 toxins, indicating that these toxins could be promising candidates for autoimmune disease therapy. Moreover, this is the first report illustrating the involvement of a novel K+ channel subtype, Kv2.1, and its distribution in T-cell subsets. (AU)

• FAPESP's process: 12/12954-6 - Study of the toxins Ts6 e Ts15 from the scorpion Tityus serrulatus as potential therapeutic drugs for the treatment of autoimmune diseases
• Grantee: Manuela Berto Pucca
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/21329-0 - Electrophysiological characterization of Tityus serrulatus venom toxins Ts3, Ts4, Ts6, Ts8, Ts15 and TS venom peptide 7: looking for new desired drugs
• Grantee: Manuela Berto Pucca
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 13/21342-7 - Electrophysiological characterization of Ts19 fragment II, a new toxin purified from Tityus serrulatus venom
• Grantee: Felipe Augusto Cerni
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 12/13590-8 - Isolation, molecular and functional characterization of a new toxin from Tityus serrulatus scorpion venom
• Grantee: Felipe Augusto Cerni
• Support Opportunities: Scholarships in Brazil - Doctorate