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-mediate...

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Published ineLife 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 Journal Article
LanguageEnglish
Published England eLife Sciences Publications Ltd 03.04.2024
eLife Sciences Publications, Ltd
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
United States > US
California
mouse
genetics
inflammation
genomics
asthma
vitamin D receptor
human
immunology
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Abstract 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.
AbstractList 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.
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.
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.
Author Halu, Arda
Bruggemann, Thayse Regina
Renz, Harald
De Marzio, Margherita
Demay, Marie
Abdulnour, Raja-Elie
Chase, Robert
Koepke, Janine
Krishnamoorthy, Nandini
Duvall, Melody G
Peh, Hong Yong
Litonjua, Augusto A
Mirzakhani, Hooman
Levy, Bruce D
Rojas Quintero, Joselyn J
Nakano, Taiji
Georgopoulos, Katia
Maiorino, Enrico
Sungur, Ayse Özge
Kilic, Ayse
Weiss, Scott T
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Keywords mouse
genetics
inflammation
genomics
asthma
vitamin D receptor
human
immunology
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License 2023, Kilic, Halu et al.
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Snippet Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma...
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Aggregation Database
Index Database
SubjectTerms 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
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Title Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1
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Volume 12
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