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

Autor: Ayse Kilic, Arda Halu, Margherita De Marzio, Enrico Maiorino, Melody G Duvall, Thayse Regina Bruggemann, Joselyn J Rojas Quintero, Robert Chase, Hooman Mirzakhani, Ayse Özge Sungur, Janine Koepke, Taiji Nakano, Hong Yong Peh, Nandini Krishnamoorthy, Raja-Elie Abdulnour, Katia Georgopoulos, Augusto A Litonjua, Marie Demay, Harald Renz, Bruce D Levy, Scott T Weiss
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: eLife, Vol 12 (2024)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.89270
Popis: 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.
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