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      Immunoregulatory Functions of the IL-12 Family of Cytokines in Antiviral Systems

      review-article
      , , *
      Viruses
      MDPI
      interleukin (IL)-12 family, viral infection, immune systems

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          Abstract

          Members of the interleukin 12 (IL-12) family have been known to be inflammatory factors since their discovery. The IL-12 family consists of IL-12, IL-23, IL-27, IL-35, and a new member, IL-39, which has recently been identified and has not yet been studied extensively. Current literature has described the mechanisms of immunity of these cytokines and potential uses for therapy and medical cures. IL-12 was found first and is effective in combatting a wide range of naturally occurring viral infections through the upregulation of various cytokines to clear the infected cells. IL-23 has an essential function in immune networks, can induce IL-17 production, and can antagonize inhibition from IL-12 in the presence of T helper (Th) 17 cells, resulting in type II IFN (IFN-γ) regulation. IL-27 has a competitive relationship to IL-35 because they both include the same subunit, the Epstein–Barr virus-induced gene3 (EBi3). This review provides a simple introduction to the IL-12 family and focuses on their functions relevant to their actions to counteract viral infections.

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          Most cited references67

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          Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes

          We have identified and purified a novel cytokine, NK cell stimulatory factor (NKSF), from the cell-free supernatant fluid of the phorbol diester-induced EBV-transformed human B lymphoblastoid cell line RPMI 8866. NKSF activity is mostly associated to a 70-kD anionic glycoprotein. The purified 70-kD protein, isolated from an SDS-PAGE gel, yields upon reduction two small species of molecular masses of 40 and 35 kD, suggesting that this cytokine is a heterodimer. When added to human PBL, purified NKSF preparations induce IFN-gamma production and synergize with rIL-2 in this activity, augment the NK cell-mediated cytotoxicity of PBL preparations against both NK-sensitive and NK- resistant target cell lines, and enhance the mitogenic response of T cells to mitogenic lectins and phorbol diesters. The three activities remain associated through different purification steps resulting in a 9,200-fold purification, and purified NKSF mediates the three biological activities at concentrations in the range of 0.1-10 pM. These data strongly suggest that the same molecule mediates these three activities, although the presence of traces of contaminant peptides even in the most purified NKSF preparations does not allow us to exclude the possibility that distinct biologically active molecules have been co-purified. The absence of other known cytokines in the purified NKSF preparations, the unusual molecular conformation of NKSF, the high specific activity of the purified protein, and the spectrum of biological activities distinguish NKSF from other previously described cytokines.
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            The Immunobiology of the Interleukin-12 Family: Room for Discovery

            The discovery of interleukin (IL)-6 and its receptor subunits provided a foundation to understand the biology of a group of related cytokines: IL-12, IL-23, IL-27. These family members utilize shared receptors and cytokine subunits and influence the outcome of cancer, infection and inflammatory diseases. Consequently, many facets of their biology are being therapeutically targeted. Here we review the landmark discoveries in this field, the combinatorial biology inherent to this family and how patient data sets have underscored the critical role of these pathways in human disease. We present significant knowledge gaps, including how similar signals from these cytokines can mediate distinct outcomes, and discuss how a better understanding of the biology of the IL-12 family provides new therapeutic opportunities. The IL-12 family of cytokines influence the outcome of cancer, infection and inflammatory diseases. Stumhofer, Hunter and Tait review the combinatorial biology inherent to this family and the recent clinical insights that underscore the critical role of these pathways in human disease.
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              The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses.

              Originally the only known heterodimeric cytokine, IL-12 is now part of a family of five cytokines and shares important functions in the regulation of both innate and adaptive immunity with two of them, IL-23 and IL-27. Although initially these three cytokines were considered to have largely overlapping immunological functions, more recent studies, including two articles in this issue of Immunity (Hamano et al., 2003; Villarino et al., 2003), indicate that they mediate complex and well-differentiated functions.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                22 August 2019
                September 2019
                : 11
                : 9
                : 772
                Affiliations
                State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China
                Author notes
                [* ]Correspondence: yingzhu@ 123456whu.edu.cn ; Tel.: +86-27-68754819; Fax: +86-27-68754592
                Article
                viruses-11-00772
                10.3390/v11090772
                6784021
                31443406
                d4490aa6-63b6-41fe-a4d4-77c84abd1c88
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 July 2019
                : 19 August 2019
                Categories
                Review

                Microbiology & Virology
                interleukin (il)-12 family,viral infection,immune systems
                Microbiology & Virology
                interleukin (il)-12 family, viral infection, immune systems

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