Expression of Human IL - 12 and In - Silico Refinement of Modified hIL - 12

Abstract

Monocytes, neutrophils, B cells, and dendritic cells create interleukin-12, a heterodimeric cytokine. In response to pathogens, phagocytic cells produce the heterodimeric protein, which consists of the two subunits p35 and p40. When IL-12 binds to the IL-12 receptor (IL-12R) on T and natural killer (NK) cells, it activates the signal transducer and activator of transcription 4 (STAT4), resulting in the creation and release of interferon-gamma (IFN-γ). Signaling downstream of IFN-γ includes the activation of the T-box transcription factor TBX21 (T-bet), which stimulates cytotoxic CD8 + T cells and NK cells as well as the production of pro-inflammatory activity in T helper 1 (TH1) cells, thereby linking innate and adaptive immunity. Following the discovery of new members of the IL-12 family, such as IL-23, which shares a subunit with IL-12, original perspectives on the relevance of IL-12 and clinical efforts to transform it into therapeutic techniques must be re-interpreted. The importance of IL-12 in immunological activity in the context of infection and (auto) inflammation, on the other hand, cannot be overstated. We'll start with an outline of the cytokine's structure and activity as well as its receptor. Recent research has demonstrated the importance of IL-12 cytokines in the development of innate and adaptive immune responses in cancer as well as the identification of multiple functions for several IL-12 family members ranging from effector to regulatory immunological activities. These cytokines have the potential to be useful Immuno-modulatory therapy options. Our research focuses on the immune response repertoire generated by the modified IL-12, which was built using a range of In silico approaches made of different web servers and software. Focusing on mutations of the p35 subunit since it is a species-specific subunit that activates the signaling cascade as well as monitoring the inflammatory response generated, i.e. IFN-γ, because low levels may not be able to showcase their effects, whilst excessive amounts induce toxicity. Furthermore, our research predicts that the modified IL-12 IFN-γ response would be lower than the usual IL-12 response, yielding lower systemic toxicity concentrations as assessed by the In-vitro approach.