A team of researchers from the National Institute of Immunology, New Delhi, Indian Institute of Technology Delhi, New Delhi, All India Institute of Medical Sciences, New Delhi, and Agency for Science, Technology, and Research (A*STAR), Singapore, has revealed how crosstalk between two molecular pathways in the cells of the gut can mediate the aberrant inflammation in Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) is a debilitating disease of the intestinal tract, plagued by chronic inflammation of the gut. A dysregulated gut immune response causes the persistent inflamed condition leading to erosion of the protective intestinal barrier.
Existing studies have shown that a series of molecular events called the NF-κB (NF-kappa B) canonical pathway plays a crucial role in triggering the immune response in the gut. Usually, the pathway controls the activity of a set of proteins called NF-κB transcription factors to regulate the inflammation process while fighting pathogens in the gut. However, in IBD, the regulation is skewed, leading to the hyperactivation of inflammatory proteins. The molecular details of what provokes this runaway process have remained elusive.
Now, a collaborative study by a team of researchers from the National Institute of Immunology, New Delhi, Indian Institute of Technology Delhi, New Delhi, All India Institute of Medical Sciences, New Delhi, and Agency for Science, Technology, and Research (A*STAR), Singapore, has deciphered a mechanism underlying the aberrant inflammation in Inflammatory Bowel Disease. The study, led by Soumen Basak, Staff Scientist VI, National Institute of Immunology, revealed unwarranted crosstalk of the canonical pathway with another seemingly harmless pathway called the noncanonical NF-κB pathway.
NF-κB is a family of transcription factors – proteins that, once activated and inside the nucleus, can bind to specific DNA regions and help transcribe (or decipher) the target genes. This subsequently generates specific proteins for physiological responses. NF-κB factors respond to a variety of signals and activate the expression of immune response genes. Their nuclear activation is controlled by two signaling pathways: canonical and noncanonical, both regulating a myriad of physiological functions.
When pathogens invade, the canonical NF-κB pathway is activated and leads to the generation of an immune response. The canonical NF-κB pathway triggers the release of cytokines and mediates a controlled inflammatory process. Once the pathogens are flushed out, the triggers subside, and the canonical pathway is inhibited.