Membrane TNFα: Importance for the Effector Function of Dendritic Cells and Potential Ways of Its Targeted Modulation

T. V. Tyrinova; S. V. Mishinov; O. Yu. Leplina; E. V. Dolgova; A. S. Proskurina; E. V. Batorov; M. A. Tikhonova; Yu. D. Kurochkina; E. A. Oleynik; A. V. Kalinovskiy; S. V. Chernov; V. V. Stupak; S. S. Bogachev; A. A. Ostanin; E. R. Chernykh

doi:10.1134/S199074781803008X

Membrane TNFα: Importance for the Effector Function of Dendritic Cells and Potential Ways of Its Targeted Modulation

Authors: Tyrinova T.V.¹, Mishinov S.V.², Leplina O.Y.¹, Dolgova E.V.³, Proskurina A.S.³, Batorov E.V.¹, Tikhonova M.A.¹, Kurochkina Y.D.¹, Oleynik E.A.¹, Kalinovskiy A.V.⁴, Chernov S.V.⁴, Stupak V.V.², Bogachev S.S.³, Ostanin A.A.¹, Chernykh E.R.¹
Affiliations:
1. Scientific Research Institute of Fundamental and Clinical Immunology
2. Scientific Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivian
3. Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences
4. Federal Neurosurgical Center
Issue: Vol 12, No 3 (2018)
Pages: 247-254
Section: Articles
URL: https://journals.rcsi.science/1990-7478/article/view/213318
DOI: https://doi.org/10.1134/S199074781803008X
ID: 213318

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Abstract

Membrane TNFα (mTNFα) is expressed on many immune cell types and performs various biological functions. Dendritic cells (DC) of high-grade glioma patients exhibit impaired cytotoxic activity against TNFα-sensitive HEp-2 tumor cells. The mechanisms leading to the impairment of the TNFα- dependent tumoricidal activity of DC and the possibility of regulating the cytotoxic activity of DC mediated by the TNFα/TNF-R1 signaling pathway have been studied. The study was conducted on healthy donors and patients with newly diagnosed high-grade glioma. DC were generated by culturing the plastic-adherent peripheral blood mononuclear cell fraction in the presence of GM-CSF and interferon-α (IFN-DC). It was shown that the impairment of the cytotoxic activity of patient IFN-DC was associated with a low number of DC expressing mTNFα and a low level of TNFα mRNA expression in DC. IFN-DC of patients exhibited a tendency of high activity of the TNFα-converting enzyme (TACE), which accomplishes shedding of mTNFα from the cell membrane. An increased number of IFN-DC with mTNFα caused by TACE blocking enhanced cytotoxic activity of the patient’s IFN-DC against HEp-2 cells. It was established that exogenous interleukin-2 and extracellular DNA are up-regulators of the mTNFα expression on IFN-DC of the patients, but their effects are mediated by different mechanisms.

Keywords

membrane TNFα, TNFα-converting enzyme, dendritic cells, interferon alpha, interleukin 2, double-stranded human DNA

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Membrane TNFα: Importance for the Effector Function of Dendritic Cells and Potential Ways of Its Targeted Modulation

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Abstract

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About the authors

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