PULMONARY PATHOLOGIES AND MANAGEMENT STRATEGIES IN PRIMARY IMMUNODEFICIENCIES

pulmonary_pathologies_kapak

EPITHELIAL BARRIER HYPOTHESIS, MICROBIOME, AND IMMUNODEFICIENCY

Tuğba Önalan

Konya Necmettin Erbakan University, Faculty of Medicine, Department of Immunology and Allergic Diseases, Konya, Türkiye

Önalan T. Epithelial Barrier Hypothesis, Microbiome, and Immunodeficiency. In: Arslan Ş editor. Pulmonary Pathologies and Management Strategies in Primary Immunodeficiencies. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.15-31.

ABSTRACT

Epithelial barriers form the first line of defense against environmental exposures and play a fundamental role in both the activation and regulation of the immune system. The “Epithelial Barrier Hypothesis” proposes that disruption of these barriers may be a central factor in the development of a wide range of diseases, including allergies, autoimmune disorders, and chronic inflammatory conditions. This chapter provides a comprehensive overview of the structural features of epithelial barriers and their bidirectional interactions with immune cells and the microbiota. Particular emphasis is placed on the characteristics of epithelial barrier defects observed in commonly encountered primary immunodeficiency (PID) subtypes and the clinical manifestations of these defects in the respiratory and gastrointestinal systems.

Mucosal barrier dysfunction not only increases susceptibility to infections but also creates a predisposition to various autoimmune and inflammatory complications. The microbiota plays a critical role in shaping immune responses by modulating the interaction between epithelial cells and the immune system through the production of bioactive molecules. In this context, microbiota-targeted interventions, cytokine-based biologic agents, growth factors that support epithelial repair, and nutrition-based supportive strategies are emerging as complementary therapeutic options in PID management. This integrative approach proposes a novel paradigm that centers not only on systemic immune dysfunction but also on local mucosal health.

Keywords: Epithelial barrier; Primary immunodeficiency; Microbiota; CVID; Bronchiectasis; Mucosal immunity

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