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

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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

DOI 10.1111/j.1365-2567.2005.02290.xPMC PMC1782241

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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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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
DOI: 10.1111/j.1365-2567.2005.02290.x
PMC: PMC1782241
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: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Immunology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Neurological Disorders and Stroke (R01NS038888)
Topics: Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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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Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice

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