Abstract

Immune dysregulation arises from a complex interplay between genetic predisposition, environmental exposures, 
and dynamic epigenetic modifications that collectively shape immune cell development, signaling, and 
responsiveness. Over the past two decades, rapid advances in genomics and epigenomics have elucidated key 
mechanisms by which inherited variants, somatic mutations, DNA methylation, histone modifications, microRNAs, 
and chromatin remodeling contribute to abnormal immune activation or suppression. These mechanisms underlie a 
wide spectrum of disorders, including autoimmunity, chronic inflammation, immunodeficiency, cancer-associated 
immune escape, and aberrant responses to infection. This review synthesizes current knowledge on major genetic 
and epigenetic determinants of immune dysregulation, highlighting the molecular pathways involved, their clinical 
significance, and the interplay between developmental and environmental influences. Emerging insights into gene
environment interactions, including the effects of diet, stress, xenobiotics, and the microbiome on immune 
epigenetics, reveal new therapeutic opportunities. Understanding how diverse layers of regulation converge on 
immune homeostasis provides a foundation for precision medicine approaches aimed at diagnosing, predicting, and 
treating diseases associated with immune imbalance.