Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules

B. Balasa, K. Van Gunst, N. Jung, D. Balakrishna, P. Santamaria, T. Hanafusa, N. Itoh, N. Sarvetnick

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Several death-signaling or death-inducing molecules have been implicated in β cell destruction, including Fas, perforin, and TNFR-1. In this study, we examined the role of each death-signaling molecule in the IL-10-accelerated diabetes of nonobese diabetic (NOD) mice. Groups of IL-10-NOD mice, each deficient in either Fas, perforin, or TNFR-1 molecules, readily developed insulitis, and subsequently succumbed to diabetes with an accelerated kinetics and incidence similar to that observed in their wild-type or heterozygous IL-10-NOD littermates. Similarly, a TNFR-2 deficiency did not block accelerated diabetes in IL-10-NOD mice and spontaneous diabetes in NOD mice. These results demonstrate that pancreatic IL-10 promotes diabetes independent of Fas, perforin, TNFR-1, and TNFR-2 molecules. Subsequently, when cyclophosphamide, a diabetes-inducing agent, was injected into insulitis-free NOD.lpr/lpr mice, none of these mice developed insulitis or diabetes. Our data suggest that cyclophosphamide-but not IL-10-induced diabetes is Fas dependent. Overall, these findings provide evidence that pancreatic expression of IL-10 promotes diabetes independent of the major death pathways and provide impetus for identification of novel death pathways precipitating autoimmune destruction of insulin-producing β cells.

Original languageEnglish (US)
Pages (from-to)2841-2849
Number of pages9
JournalJournal of Immunology
Volume165
Issue number5
DOIs
StatePublished - Sep 1 2000

Fingerprint

Perforin
Inbred NOD Mouse
Tumor Necrosis Factor Receptors
Interleukin-10
Cyclophosphamide
Insulin
Incidence

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules. / Balasa, B.; Van Gunst, K.; Jung, N.; Balakrishna, D.; Santamaria, P.; Hanafusa, T.; Itoh, N.; Sarvetnick, N.

In: Journal of Immunology, Vol. 165, No. 5, 01.09.2000, p. 2841-2849.

Research output: Contribution to journalArticle

Balasa, B. ; Van Gunst, K. ; Jung, N. ; Balakrishna, D. ; Santamaria, P. ; Hanafusa, T. ; Itoh, N. ; Sarvetnick, N. / Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules. In: Journal of Immunology. 2000 ; Vol. 165, No. 5. pp. 2841-2849.
@article{3f4142b0ea0041978f0cbf3d6ed05297,
title = "Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules",
abstract = "Several death-signaling or death-inducing molecules have been implicated in β cell destruction, including Fas, perforin, and TNFR-1. In this study, we examined the role of each death-signaling molecule in the IL-10-accelerated diabetes of nonobese diabetic (NOD) mice. Groups of IL-10-NOD mice, each deficient in either Fas, perforin, or TNFR-1 molecules, readily developed insulitis, and subsequently succumbed to diabetes with an accelerated kinetics and incidence similar to that observed in their wild-type or heterozygous IL-10-NOD littermates. Similarly, a TNFR-2 deficiency did not block accelerated diabetes in IL-10-NOD mice and spontaneous diabetes in NOD mice. These results demonstrate that pancreatic IL-10 promotes diabetes independent of Fas, perforin, TNFR-1, and TNFR-2 molecules. Subsequently, when cyclophosphamide, a diabetes-inducing agent, was injected into insulitis-free NOD.lpr/lpr mice, none of these mice developed insulitis or diabetes. Our data suggest that cyclophosphamide-but not IL-10-induced diabetes is Fas dependent. Overall, these findings provide evidence that pancreatic expression of IL-10 promotes diabetes independent of the major death pathways and provide impetus for identification of novel death pathways precipitating autoimmune destruction of insulin-producing β cells.",
author = "B. Balasa and {Van Gunst}, K. and N. Jung and D. Balakrishna and P. Santamaria and T. Hanafusa and N. Itoh and N. Sarvetnick",
year = "2000",
month = "9",
day = "1",
doi = "10.4049/jimmunol.165.5.2841",
language = "English (US)",
volume = "165",
pages = "2841--2849",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Islet-specific expression of IL-10 promotes diabetes in nonobese diabetic mice independent of Fas, perforin, TNF receptor-1, and TNF receptor-2 molecules

AU - Balasa, B.

AU - Van Gunst, K.

AU - Jung, N.

AU - Balakrishna, D.

AU - Santamaria, P.

AU - Hanafusa, T.

AU - Itoh, N.

AU - Sarvetnick, N.

PY - 2000/9/1

Y1 - 2000/9/1

N2 - Several death-signaling or death-inducing molecules have been implicated in β cell destruction, including Fas, perforin, and TNFR-1. In this study, we examined the role of each death-signaling molecule in the IL-10-accelerated diabetes of nonobese diabetic (NOD) mice. Groups of IL-10-NOD mice, each deficient in either Fas, perforin, or TNFR-1 molecules, readily developed insulitis, and subsequently succumbed to diabetes with an accelerated kinetics and incidence similar to that observed in their wild-type or heterozygous IL-10-NOD littermates. Similarly, a TNFR-2 deficiency did not block accelerated diabetes in IL-10-NOD mice and spontaneous diabetes in NOD mice. These results demonstrate that pancreatic IL-10 promotes diabetes independent of Fas, perforin, TNFR-1, and TNFR-2 molecules. Subsequently, when cyclophosphamide, a diabetes-inducing agent, was injected into insulitis-free NOD.lpr/lpr mice, none of these mice developed insulitis or diabetes. Our data suggest that cyclophosphamide-but not IL-10-induced diabetes is Fas dependent. Overall, these findings provide evidence that pancreatic expression of IL-10 promotes diabetes independent of the major death pathways and provide impetus for identification of novel death pathways precipitating autoimmune destruction of insulin-producing β cells.

AB - Several death-signaling or death-inducing molecules have been implicated in β cell destruction, including Fas, perforin, and TNFR-1. In this study, we examined the role of each death-signaling molecule in the IL-10-accelerated diabetes of nonobese diabetic (NOD) mice. Groups of IL-10-NOD mice, each deficient in either Fas, perforin, or TNFR-1 molecules, readily developed insulitis, and subsequently succumbed to diabetes with an accelerated kinetics and incidence similar to that observed in their wild-type or heterozygous IL-10-NOD littermates. Similarly, a TNFR-2 deficiency did not block accelerated diabetes in IL-10-NOD mice and spontaneous diabetes in NOD mice. These results demonstrate that pancreatic IL-10 promotes diabetes independent of Fas, perforin, TNFR-1, and TNFR-2 molecules. Subsequently, when cyclophosphamide, a diabetes-inducing agent, was injected into insulitis-free NOD.lpr/lpr mice, none of these mice developed insulitis or diabetes. Our data suggest that cyclophosphamide-but not IL-10-induced diabetes is Fas dependent. Overall, these findings provide evidence that pancreatic expression of IL-10 promotes diabetes independent of the major death pathways and provide impetus for identification of novel death pathways precipitating autoimmune destruction of insulin-producing β cells.

UR - http://www.scopus.com/inward/record.url?scp=0034284446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034284446&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.165.5.2841

DO - 10.4049/jimmunol.165.5.2841

M3 - Article

C2 - 10946317

AN - SCOPUS:0034284446

VL - 165

SP - 2841

EP - 2849

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -