Reverse Genetics Applied to Immunobiology of Tumor Necrosis Factor, a Multifunctional Cytokine.

Tumor necrosis factor (TNF) is one of many cytokines - protein molecules responsible for communication between the cells of immune system. TNF was discovered and given its grand name because of its striking antitumor effects in experimental systems, but its main physiological functions in the context of whole organism turned out to be completely unrelated to protection against tumors. This short review discusses "man-made" mouse models generated by early genome-editing technologies, which enabled us to establish true functions of TNF in health and certain diseases as well as to unravel potential strategies for improving therapy of TNF-dependent diseases.

Transcriptional Regulation of the Gene, Encoding p40 Subunit of IL-12 and IL-23, in Murine Macrophages.

Interleukin-12 (IL-12) is an immunomodulatory cytokine with broad spectrum of activities, central of which are stimulation of NK cells, and promoting differentiation of T helper cells towards Th1 phenotype. IL-12 consists of two unrelated subunits, p35 and p40. Recently discovered cytokine, IL-23, which has both unique properties and those overlapping with IL-12, also contains p40 associated with another subunit, p19. Both IL-12 and IL-23 transmit the signal through receptors associated with JAK-STAT pathways. One of the critical components in the control of both IL-12 and IL-23 regulation is the transcriptional control of p40 gene which is induced in macrophages and dendritic cells in response to bacterial endotoxin, IFN-gamma and other stimuli. In the present study we report on the structure of the transcriptional unit of the murine p40 gene, its promoter and inducible expression of p40 in murine macrophages. Our findings are consistent with multi-level regulation of p40 expression.