Chapters authored
The Cellular Stress Response Interactome and Extracellular Matrix Cross-Talk during Fibrosis: A Stressed Extra-Matrix Affair
Diverse internal and external pathologic stimuli can trigger cellular stress response pathways (CSRPs) that are usually counteracted by intrinsic homeostatic machinery, which responds to stress by initiating complex signaling mechanisms to eliminate either the stressor or the damaged cells. There is growing evidence that CSRPs can have context-dependent homeostatic or pathologic functions that may result in tissue fibrosis under persistence of stress. CSRPs can drive intercellular communications through exosomes (trafficking and secretory pathway determinants) secreted in response to stress-induced proteostasis rebalancing. The injured tissue environment upon sensing the stress turns on a precisely orchestrated network of immune responses by regulating cytokine-chemokine production, recruitment of immune cells, and modulating fibrogenic niche and extracellular matrix (ECM) cross-talk during fibrotic pathologies like cardiac fibrosis, liver fibrosis, laryngotracheal stenosis, systemic scleroderma, interstitial lung disease and inflammatory bowel disease. Immunostimulatory RNAs (like double stranded RNAs) generated through deregulated RNA processing pathways along with RNA binding proteins (RBPs) of RNA helicase (RNA sensors) family are emerging as important components of immune response pathways during sterile inflammation. The paradigm-shift in RNA metabolism associated interactome has begun to offer new therapeutic windows by unravelling the novel RBPs and splicing factors in context of developmental and fibrotic pathways. We would like to review emerging regulatory nodes and their interaction with CSRPs, and tissue remodeling with major focus on cardiac fibrosis, and inflammatory responses underlying upper airway fibrosis.
Part of the book: Extracellular Matrix
Th17/IL-17, Immunometabolism and Psoriatic Disease: A Pathological Trifecta
The burgeoning arena of immunometabolism provides evidence of how cellular, as well as local (tissue)/systemic metabolic pathways, are playing an important role in controlling immunity and inflammation. An intricate and elaborate network of various metabolic circuits specifically glycolysis, fatty acid oxidation and synthesis and amino acid metabolism precisely generate metabolites that rewire the immune response. Psoriasis is a chronic progressive self-perpetuated “IL-17-centric” inflammatory disease characterized by the co-existence of autoimmune and autoinflammatory pathways. Metabolic responses, governed by oxygen levels, nutrient availability, growth factors, cytokines, AMP/ATP ratios and amino acids, play a pivotal role in programming Th17 cell fate determination. Understanding the intricate interactions and complex interplay of molecular mechanisms responsible for Th17 cell metabolic rewiring, an important determinant of Th17 cell plasticity and heterogeneity, holds the potential to reshape psoriatic therapeutics in ways currently unimagined. This chapter entails with most recent updates on major cellular and systemic metabolic pathways regulating differentiation of Th17 cells as well their cross-talk with intracellular signaling mediators and also sheds light on how dysregulation of these pathways can be responsible for immune impairment and development of psoriatic disease. A better understanding of these metabolic processes could unveil an intriguing leverage point for therapeutic interventions to modulate metabolic programming and Th17 cell responses in this multi-systemic inflammatory disease.
Part of the book: Psoriasis