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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 Thaís B.,
Cerni Felipe A.,
Bordon Karla C. F.,
Peigneur Steve,
Tytgat Jan,
Bonato Vânia L.,
Arantes Eliane C.
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12559
Subject(s) - effector , biology , cd8 , t cell , in vivo , cytotoxic t cell , immunology , microbiology and biotechnology , potassium channel , pathogenesis , in vitro , antigen , immune system , biochemistry , genetics , biophysics
Summary 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 CD 4 + cell subsets: naive, effector ( T EF ), central memory ( T CM ) and effector memory ( T EM ). The electrophysiological 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‐ γ production; however, Ts15 also inhibits other CD 4 + cell subsets (naive, T EF and T CM ). Based on the Ts15 inhibitory effect of proliferation of all CD 4 + cell subsets, and based on its blocking effect on Kv2.1, we investigated the Kv2.1 expression in T cells. The assays showed that CD 4 + and CD 8 + 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.