Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice

V. Dugas, A. Liston, E. E. Hillhouse, R. Collin, G. Chabot-Roy, A. N. Pelletier, C. Beauchamp, Kris HARDY, S. Lesage

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Immunoregulatory T cells have been identified as key modulators of peripheral tolerance and participate in preventing autoimmune diseases. CD4 - CD8 - (double negative, DN) T cells compose one of these immunoregulatory T-cell subsets, where the injection of DN T cells confers protection from autoimmune diabetes progression. Interestingly, genetic loci defining the function and number of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) coincide with at least some autoimmune disease susceptibility loci. Herein, we investigate the impact of major insulin-dependent diabetes (Idd) loci in defining the number of DN T cells. We demonstrate that although Idd3, Idd5 and Idd9 loci do not regulate DN T-cell number, NOD mice congenic for diabetes resistance alleles at the Idd13 locus show a partial restoration in DN T-cell number. Moreover, competitive and non-competitive bone marrow chimera experiments reveal that DN T-cell number is defined by a bone marrow-intrinsic, but DN T-cell-extrinsic, factor. This suggests that non-autonomous candidate genes define DN T-cell number in secondary lymphoid organs. Together, our results show that the regulation of DN T-cell number in NOD mice is at least partially conferred by alleles at the Idd13 locus.

Original languageEnglish
Pages (from-to)82-87
Number of pages6
JournalGenes and Immunity
Volume15
Issue number2
DOIs
Publication statusPublished - 2014

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Inbred NOD Mouse
Cell Count
T-Lymphocytes
Autoimmune Diseases
Bone Marrow
Alleles
Peripheral Tolerance
TCF Transcription Factors
Genetic Loci
Cytoprotection
Disease Susceptibility
T-Lymphocyte Subsets
Regulatory T-Lymphocytes
Type 1 Diabetes Mellitus
Insulin
Injections

Cite this

Dugas, V., Liston, A., Hillhouse, E. E., Collin, R., Chabot-Roy, G., Pelletier, A. N., ... Lesage, S. (2014). Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice. Genes and Immunity, 15(2), 82-87. https://doi.org/10.1038/gene.2013.65
Dugas, V. ; Liston, A. ; Hillhouse, E. E. ; Collin, R. ; Chabot-Roy, G. ; Pelletier, A. N. ; Beauchamp, C. ; HARDY, Kris ; Lesage, S. / Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice. In: Genes and Immunity. 2014 ; Vol. 15, No. 2. pp. 82-87.
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Dugas, V, Liston, A, Hillhouse, EE, Collin, R, Chabot-Roy, G, Pelletier, AN, Beauchamp, C, HARDY, K & Lesage, S 2014, 'Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice', Genes and Immunity, vol. 15, no. 2, pp. 82-87. https://doi.org/10.1038/gene.2013.65

Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice. / Dugas, V.; Liston, A.; Hillhouse, E. E.; Collin, R.; Chabot-Roy, G.; Pelletier, A. N.; Beauchamp, C.; HARDY, Kris; Lesage, S.

In: Genes and Immunity, Vol. 15, No. 2, 2014, p. 82-87.

Research output: Contribution to journalArticle

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AU - Dugas, V.

AU - Liston, A.

AU - Hillhouse, E. E.

AU - Collin, R.

AU - Chabot-Roy, G.

AU - Pelletier, A. N.

AU - Beauchamp, C.

AU - HARDY, Kris

AU - Lesage, S.

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AB - Immunoregulatory T cells have been identified as key modulators of peripheral tolerance and participate in preventing autoimmune diseases. CD4 - CD8 - (double negative, DN) T cells compose one of these immunoregulatory T-cell subsets, where the injection of DN T cells confers protection from autoimmune diabetes progression. Interestingly, genetic loci defining the function and number of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) coincide with at least some autoimmune disease susceptibility loci. Herein, we investigate the impact of major insulin-dependent diabetes (Idd) loci in defining the number of DN T cells. We demonstrate that although Idd3, Idd5 and Idd9 loci do not regulate DN T-cell number, NOD mice congenic for diabetes resistance alleles at the Idd13 locus show a partial restoration in DN T-cell number. Moreover, competitive and non-competitive bone marrow chimera experiments reveal that DN T-cell number is defined by a bone marrow-intrinsic, but DN T-cell-extrinsic, factor. This suggests that non-autonomous candidate genes define DN T-cell number in secondary lymphoid organs. Together, our results show that the regulation of DN T-cell number in NOD mice is at least partially conferred by alleles at the Idd13 locus.

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Dugas V, Liston A, Hillhouse EE, Collin R, Chabot-Roy G, Pelletier AN et al. Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice. Genes and Immunity. 2014;15(2):82-87. https://doi.org/10.1038/gene.2013.65