Literature Review: Molecular and Immunology Aspect of Crohns’s Disease Pathophysiology

Abstract

Crohn's Disease (CD) is a chronic inflammatory bowel disease characterized by transmural inflammation that can affect any part of the gastrointestinal tract, especially the terminal ileum and colon. It is distinguished by segmental inflammation, or "skip lesions," which separates healthy regions from inflamed areas. The pathophysiology of CD is driven by dysregulated immune responses to gut microbiota, particularly involving T-helper (Th) 1 and Th17 cells, as well as innate immune cells like macrophages and neutrophils. These immune cells release pro-inflammatory cytokines such as TNF-α and IL-17, which increase intestinal permeability and exacerbate tissue damage. Genetic factors, including mutations in the NOD2 and IL-23R genes, contribute to disease susceptibility by impairing pathogen recognition and promoting overactivation of inflammatory responses. The inflammation leads to structural changes in the intestinal wall, including thickening, fibrosis, and the formation of fistulas and non-caseating granulomas. These changes result in clinical symptoms such as chronic diarrhea, abdominal pain, malabsorption, and weight loss. Extra-intestinal manifestations like peripheral arthritis and skin conditions are also common, reflecting systemic immune involvement. Dysbiosis, or an imbalance in gut microbiota, worsens inflammation by promoting the growth of pathogenic bacteria and impairing mucosal barrier function. The complex interactions among immune responses, genetic factors, and microbiota drive the progression of CD, highlighting the need for targeted therapies to manage the disease effectively.