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Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse.
Physiol Genomics. 2005 Apr 14; 21(2):201-11.PG

Abstract

In type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, the pathogenic destruction of the insulin-producing pancreatic beta-cells is under the control of and influenced by distinct subsets of T lymphocytes. To identify the critical genes expressed by autoimmune T cells, antigen presenting cells, and pancreatic beta-cells during the evolution of T1DM in the nonobese diabetic (NOD) mouse, and the genetically-altered NOD mouse (BDC/N), we used functional genomics. Microarray analysis revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin (IL)-17, and islet cell regenerating genes, Reg3alpha, Reg3beta, and Reg3gamma. Our data indicate that progression to insulitis was connected to marked changes in islet antigen expression, beta-cell differentiation, and T cell activation and signaling, all associated with tumor necrosis factor-alpha and IL-6 expression. Overt diabetes saw a clear shift in cytokine, chemokine, and T cell differentiation factor expression, consistent with a focused Th1 response, as well as a significant upregulation in genes associated with cellular adhesion, homing, and apoptosis. Importantly, the temporal pattern of expression of key verified genes suggested that T1DM develops in a relapsing/remitting as opposed to a continuous fashion, with insulitis linked to hypoxia-regulated gene control and diabetes with C/EBP and Nkx2 gene control.

Authors+Show Affiliations

Diabetes Research Center, Division of Endocrinology, Cincinnati Children's Hospital Research Foundation and College of Medicine, University of Cincinnati, Cincinnati, Ohio 45229-3039, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15671250

Citation

Vukkadapu, Sankaranand S., et al. "Dynamic Interaction Between T Cell-mediated Beta-cell Damage and Beta-cell Repair in the Run Up to Autoimmune Diabetes of the NOD Mouse." Physiological Genomics, vol. 21, no. 2, 2005, pp. 201-11.
Vukkadapu SS, Belli JM, Ishii K, et al. Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse. Physiol Genomics. 2005;21(2):201-11.
Vukkadapu, S. S., Belli, J. M., Ishii, K., Jegga, A. G., Hutton, J. J., Aronow, B. J., & Katz, J. D. (2005). Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse. Physiological Genomics, 21(2), 201-11.
Vukkadapu SS, et al. Dynamic Interaction Between T Cell-mediated Beta-cell Damage and Beta-cell Repair in the Run Up to Autoimmune Diabetes of the NOD Mouse. Physiol Genomics. 2005 Apr 14;21(2):201-11. PubMed PMID: 15671250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse. AU - Vukkadapu,Sankaranand S, AU - Belli,Jenine M, AU - Ishii,Koji, AU - Jegga,Anil G, AU - Hutton,John J, AU - Aronow,Bruce J, AU - Katz,Jonathan D, Y1 - 2005/01/25/ PY - 2005/1/27/pubmed PY - 2006/6/8/medline PY - 2005/1/27/entrez SP - 201 EP - 11 JF - Physiological genomics JO - Physiol Genomics VL - 21 IS - 2 N2 - In type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, the pathogenic destruction of the insulin-producing pancreatic beta-cells is under the control of and influenced by distinct subsets of T lymphocytes. To identify the critical genes expressed by autoimmune T cells, antigen presenting cells, and pancreatic beta-cells during the evolution of T1DM in the nonobese diabetic (NOD) mouse, and the genetically-altered NOD mouse (BDC/N), we used functional genomics. Microarray analysis revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin (IL)-17, and islet cell regenerating genes, Reg3alpha, Reg3beta, and Reg3gamma. Our data indicate that progression to insulitis was connected to marked changes in islet antigen expression, beta-cell differentiation, and T cell activation and signaling, all associated with tumor necrosis factor-alpha and IL-6 expression. Overt diabetes saw a clear shift in cytokine, chemokine, and T cell differentiation factor expression, consistent with a focused Th1 response, as well as a significant upregulation in genes associated with cellular adhesion, homing, and apoptosis. Importantly, the temporal pattern of expression of key verified genes suggested that T1DM develops in a relapsing/remitting as opposed to a continuous fashion, with insulitis linked to hypoxia-regulated gene control and diabetes with C/EBP and Nkx2 gene control. SN - 1531-2267 UR - https://www.unboundmedicine.com/medline/citation/15671250/Dynamic_interaction_between_T_cell_mediated_beta_cell_damage_and_beta_cell_repair_in_the_run_up_to_autoimmune_diabetes_of_the_NOD_mouse_ L2 - https://journals.physiology.org/doi/abs/10.1152/physiolgenomics.00173.2004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -