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

• Published in: eLife 2024-04, Vol.12
• Main Authors: Kilic, Ayse, Halu, Arda, De Marzio, Margherita, Maiorino, Enrico, Duvall, Melody G, Bruggemann, Thayse Regina, Rojas Quintero, Joselyn J, Chase, Robert, Mirzakhani, Hooman, Sungur, Ayse Özge, Koepke, Janine, Nakano, Taiji, Peh, Hong Yong, Krishnamoorthy, Nandini, Abdulnour, Raja-Elie, Georgopoulos, Katia, Litonjua, Augusto A, Demay, Marie, Renz, Harald, Levy, Bruce D, Weiss, Scott T
• Format: Article
• Language: English
• Subjects: Animals; Asthma; Autoimmune diseases; Binding sites; CD4 antigen; Dietary supplements; Disease; Gene loci; Genetics and Genomics; Genomes; Genotype & phenotype; Helper cells; Humans; Immune system; Immunology and Inflammation; Immunomodulation; Immunoregulation; Inflammation; Inflammatory diseases; Interleukin 2; Lymphocytes T; Mice; Pneumonia; Polymorphism; Pregnancy; Prenatal experience; Stat5 protein; Th2 Cells; Vitamin D; Vitamin D - pharmacology; Vitamin D Deficiency - metabolism; vitamin D receptor; Vitamin D receptors; Vitamin deficiency; Vitamins; Womens health
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.89270

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 ( ) 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 -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.