page_title: Transflammation
section_title: Transflammation process
hierarchical_section_title: Transflammation / Transflammation process
caption_attribution_description: English: During reprogramming of cells with viral vectors, TLR3 is activated and innate immune response is triggered. Subsequent activation of NFκβ and the associated formation of oxygen radicals is involved in chromatin remodeling and facilitates the introduction of transcription factors (OSKM) on the genes.
context_page_description: Transflamation describes the process by which innate immune response mechanisms affect the epigenetic plasticity of a cell during nuclear reprogramming. This phenomenon is essential in dedifferentiating a somatic cell to a pluripotent cell and also in transdifferentiating a terminally differentiated cell to another terminally differentiated cell.
context_section_description: The viral vector stimulates pattern recognotion receptors (PRR): toll like receptors (TLRs) or RL-I-like receptors (RLRs), which trigger anti-inflammatory signaling of innate immunity and subsequently activate transcription factors NF-κβ and IRF3. These factors are involved in chromatin remodeling in the nucleus. The result is chromatin release and facilitating transcription factors to bind the genes.
  Signalling via oxygen and nitrogen radicals (ROS, NOS) enhance the inflammatory response by generating additional danger associated molecular pattern (DAMP) is also involved in successful cell reprogramming. Inducible NO synthase (iNOS) is responsible for the generation of nitrogen radicals in the cell and it is activated after binding of NF-κβ to promoter.
  iPSC forms oxygen radicals only in the initial phase of reprogramming. Later oxidation activity attenuates and up-regulation of antioxidant enzymes occurs. The correct timing and amount of ROS / NOS is critical to the overall efficiency of the process. A cell stimulated with poly I: C (a synthetic TLR3 receptor agonist) with low doses of poly I: C increase iPSC production but higher levels decrease IPSC. It means if the innate immune response is inhibited or the response is disproportionately large, the cell will not be reprogrammed („Goldilocks zone“).
caption: Transflammation scheme
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