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

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Pucca, Manuela B. ; Bertolini, Thais B. ; Cerni, Felipe A. ; Bordon, Karla C. F. ; Peigneur, Steve ; Tytgat, Jan ; Bonato, Vania L. ; Arantes, Eliane C.
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: IMMUNOLOGY; v. 147, n. 2, p. 11-pg., 2016-02-01.

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)

Processo FAPESP: 12/12954-6 - Estudo das toxinas Ts6 e Ts15 do escorpião Tityus serrulatus como potenciais drogas terapêuticas para o tratamento de doenças autoimunes
Beneficiário:Manuela Berto Pucca
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 13/21329-0 - Caracterização eletrofisiológica das toxinas provenientes da peçonha de Tityus serrulatus Ts3, Ts4, Ts6, Ts8, Ts15 e TS venom peptide 7: busca de novas drogas terapêuticas
Beneficiário:Manuela Berto Pucca
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
Processo FAPESP: 13/21342-7 - Caracterização eletrofisiológica da Ts19 fragmento II, uma nova toxina purificada da peçonha de Tityus serrulatus
Beneficiário:Felipe Augusto Cerni
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
Processo FAPESP: 12/13590-8 - Isolamento, caracterização molecular e funcional de uma nova toxina presente na peçonha do escorpião Tityus serrulatus.
Beneficiário:Felipe Augusto Cerni
Modalidade de apoio: Bolsas no Brasil - Doutorado