Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.

Specialized pro-resolving mediators in respiratory diseases.

PURPOSE OF REVIEW: Persistent unresolved inflammation results in a number of pathologic respiratory diseases including asthma, cystic fibrosis, acute respiratory distress syndrome (ARDS) and coronavirus disease 2019 (COVID-19)-associated ARDS. Inflammation resolution is an active series of biologic processes orchestrated by a family of bioactive specialized pro-resolving mediators (SPMs) derived from essential omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). In this review, we highlight recent findings on dysregulated inflammation resolution in common respiratory diseases and recent literature on SPM generation with PUFA dietary supplementation with relevance to diseases of respiratory inflammation. RECENT FINDINGS: Human studies and preclinical models of diseases of lung inflammation have revealed disequilibrium in the levels of pro-inflammatory versus pro-resolving mediators. Recent studies identified actions for SPMs on regulating prophlogistic host responses and stimulating inflammation resolution pathways in inflammatory respiratory diseases. SUMMARY: Dietary marine oils are enriched in PUFAs and contain parent omega-3 and omega-6 fatty acids and precursors for conversion to SPMs. Nutritional supplementation with fish oils can boost SPM levels and offer a therapeutic approach targeting inflammation resolution pathways for diseases of lung inflammation.