Cited by 128Inflammatory Bowel DiseaseVitamin D Research StudiesT-cell and B-cell Immunology

Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice

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Froicu, Monica, Zhu, Yan, Cantorna, Margherita T.·2006·Immunology

Abstract

The vitamin D receptor (VDR) is a nuclear receptor expressed in a number of different cells of the immune system. This study was performed to determine the effect of VDR deficiency on immune function and inflammation of the gastrointestinal tract in a model of inflammatory bowel disease, namely interleukin-10 (IL-10) knockout mice. IL-10 knockout mice were generated which either could or could not respond to vitamin D (double IL-10/VDR knockout; DKO). The distribution and function of lymphocytes in both the primary and secondary lymphoid organs were compared and determined as a function of the severity of intestinal inflammation. DKO mice had normal thymic development and peripheral T-cell numbers at 3 weeks of age, but a week after intestinal disease was detected the thymus was dysplastic with a reduction in cellularity. The atrophy was coupled with increased apoptosis. The spleen weight of DKO mice increased as a result of the accumulation of red blood cells; however, there was a 50% reduction in the numbers of T and B cells. Conversely, the mesenteric lymph nodes were enlarged and contained increased numbers of lymphocytes. The T cells from DKO mice were of a memory phenotype and were hyporesponsive to T-cell receptor stimulation. Colitis in the DKO mice was associated with local and high expression of IL-2, interferon-gamma, IL-1beta, tumour necrosis factor-alpha and IL-12. The primary and secondary lymphoid organs in DKO mice are profoundly altered as a consequence of the fulminating inflammation in the gastrointestinal tract. VDR expression is required for the T cells and other immune cells to control inflammation in the IL-10 KO mice.

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Crossref · 10.1111/j.1365-2567.2005.02290.x

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Authors
Froicu, M., Zhu, Y., & Cantorna, M. T.
Affiliations
Pennsylvania State University (US)
Corresponding author
Cantorna, Margherita T.
Venue
Immunology
Publisher
Wiley
Published
2006-02-13
Volume
117
Issue
3
Pages
310-318
ISSN
  • 0019-2805 (ISSN-L)
  • 1365-2567
OpenAlex
W2101825351
Cited by
128
References
30
Citations by year
2026: 2 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 2 · 2020: 6 · 2019: 9 · 2018: 5 · 2017: 5 · 2016: 10 · 2015: 11 · 2014: 9 · 2013: 7 · 2012: 5
FWCI
3.01
Type
journal article
Language
en
Open access
Locations
  • Immunology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS038888)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
vitamin D receptor, IL-10 knockout mice, inflammatory bowel disease, colitis, intestinal immunity, thymic atrophy, T cell hyporesponsiveness, mesenteric lymph nodes, lymphocyte distribution, secondary lymphoid organs, cytokine expression, thymic apoptosis
MeSH terms
Animals, Atrophy, Colon, Disease Models, Animal, Flow Cytometry, Lymphoid Tissue, Mice, Inbred C57BL, Thymus Gland, Inflammatory Bowel Diseases, T-Lymphocyte Subsets, Cytokines, Interleukin-10, Apoptosis, Receptors, Calcitriol, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Mice

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