IL-10-deficiency unmasks unique immune system defects and reveals differential regulation of organ-specific autoimmunity in non-obese diabetic mice

Govindarajan Rajagopalan, Yogish C Kudva, Moon M. Sen, Eric V. Marietta, Narayana Murali, Karl A Nath, Jodi Moore, Chella S. David

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Interleukin (IL)-10 is a potent anti-inflammatory cytokine and ablation of IL-10 exacerbates Th1-type autoimmune diseases. Even though type 1 diabetes (T1D) in NOD mice is believed to be Th1-mediated, the incidence and severity of T1D is unaltered in IL-10-deficient NOD mice raised under pathogen-free conditions. We describe for the first time, the outcome of IL-10 deficiency on islet and other organ-specific autoimmunity in NOD mice raised in a conventional facility. IL-10-deficient NOD mice under such conditions were protected from spontaneous as well as cyclophosphamide-induced diabetes, but were susceptible to diabetes induced by adoptive transfer of splenocytes from spontaneously diabetic NOD mice. Whereas the incidence of rectal prolapse was very high in this NOD.IL-10-/- mouse colony, IL-10-deficient C57Bl/6 mice raised under similar conditions seldom developed rectal prolapse. While injection of complete Freund's adjuvant (CFA) significantly reduced insulitis, it did not ameliorate colitis in IL-10-deficient NOD mice indicating differential regulation of organ-specific autoimmunity by CFA. Phenotypic characterization of IL-10-/- mice revealed a significant increase in splenic macrophage numbers in NOD but not on the B6 background. This was accompanied by a heightened systemic inflammatory cytokine response and mortality following in vivo challenge with a toll-like receptor 9 agonist, CpG-containing DNA.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalCytokine
Volume34
Issue number1-2
DOIs
StatePublished - Apr 21 2006

Fingerprint

Inbred NOD Mouse
Immune system
Autoimmunity
Interleukin-10
Immune System
Defects
Medical problems
Rectal Prolapse
Freund's Adjuvant
Type 1 Diabetes Mellitus
Toll-Like Receptor 9
Cytokines
Adoptive Transfer
Macrophages
Incidence
Pathogens
Colitis
Ablation
Cyclophosphamide
Autoimmune Diseases

Keywords

  • Autoimmunity
  • Colitis and rectal prolapse
  • Cytokine
  • Diabetes
  • IL-10
  • Knockout mice
  • Non-obese diabetic mice
  • Rodents
  • Type 1 diabetes

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

IL-10-deficiency unmasks unique immune system defects and reveals differential regulation of organ-specific autoimmunity in non-obese diabetic mice. / Rajagopalan, Govindarajan; Kudva, Yogish C; Sen, Moon M.; Marietta, Eric V.; Murali, Narayana; Nath, Karl A; Moore, Jodi; David, Chella S.

In: Cytokine, Vol. 34, No. 1-2, 21.04.2006, p. 85-95.

Research output: Contribution to journalArticle

Rajagopalan, Govindarajan ; Kudva, Yogish C ; Sen, Moon M. ; Marietta, Eric V. ; Murali, Narayana ; Nath, Karl A ; Moore, Jodi ; David, Chella S. / IL-10-deficiency unmasks unique immune system defects and reveals differential regulation of organ-specific autoimmunity in non-obese diabetic mice. In: Cytokine. 2006 ; Vol. 34, No. 1-2. pp. 85-95.
@article{96320b64ce9d4959886fefb2213b23b8,
title = "IL-10-deficiency unmasks unique immune system defects and reveals differential regulation of organ-specific autoimmunity in non-obese diabetic mice",
abstract = "Interleukin (IL)-10 is a potent anti-inflammatory cytokine and ablation of IL-10 exacerbates Th1-type autoimmune diseases. Even though type 1 diabetes (T1D) in NOD mice is believed to be Th1-mediated, the incidence and severity of T1D is unaltered in IL-10-deficient NOD mice raised under pathogen-free conditions. We describe for the first time, the outcome of IL-10 deficiency on islet and other organ-specific autoimmunity in NOD mice raised in a conventional facility. IL-10-deficient NOD mice under such conditions were protected from spontaneous as well as cyclophosphamide-induced diabetes, but were susceptible to diabetes induced by adoptive transfer of splenocytes from spontaneously diabetic NOD mice. Whereas the incidence of rectal prolapse was very high in this NOD.IL-10-/- mouse colony, IL-10-deficient C57Bl/6 mice raised under similar conditions seldom developed rectal prolapse. While injection of complete Freund's adjuvant (CFA) significantly reduced insulitis, it did not ameliorate colitis in IL-10-deficient NOD mice indicating differential regulation of organ-specific autoimmunity by CFA. Phenotypic characterization of IL-10-/- mice revealed a significant increase in splenic macrophage numbers in NOD but not on the B6 background. This was accompanied by a heightened systemic inflammatory cytokine response and mortality following in vivo challenge with a toll-like receptor 9 agonist, CpG-containing DNA.",
keywords = "Autoimmunity, Colitis and rectal prolapse, Cytokine, Diabetes, IL-10, Knockout mice, Non-obese diabetic mice, Rodents, Type 1 diabetes",
author = "Govindarajan Rajagopalan and Kudva, {Yogish C} and Sen, {Moon M.} and Marietta, {Eric V.} and Narayana Murali and Nath, {Karl A} and Jodi Moore and David, {Chella S.}",
year = "2006",
month = "4",
day = "21",
doi = "10.1016/j.cyto.2006.04.006",
language = "English (US)",
volume = "34",
pages = "85--95",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
number = "1-2",

}

TY - JOUR

T1 - IL-10-deficiency unmasks unique immune system defects and reveals differential regulation of organ-specific autoimmunity in non-obese diabetic mice

AU - Rajagopalan, Govindarajan

AU - Kudva, Yogish C

AU - Sen, Moon M.

AU - Marietta, Eric V.

AU - Murali, Narayana

AU - Nath, Karl A

AU - Moore, Jodi

AU - David, Chella S.

PY - 2006/4/21

Y1 - 2006/4/21

N2 - Interleukin (IL)-10 is a potent anti-inflammatory cytokine and ablation of IL-10 exacerbates Th1-type autoimmune diseases. Even though type 1 diabetes (T1D) in NOD mice is believed to be Th1-mediated, the incidence and severity of T1D is unaltered in IL-10-deficient NOD mice raised under pathogen-free conditions. We describe for the first time, the outcome of IL-10 deficiency on islet and other organ-specific autoimmunity in NOD mice raised in a conventional facility. IL-10-deficient NOD mice under such conditions were protected from spontaneous as well as cyclophosphamide-induced diabetes, but were susceptible to diabetes induced by adoptive transfer of splenocytes from spontaneously diabetic NOD mice. Whereas the incidence of rectal prolapse was very high in this NOD.IL-10-/- mouse colony, IL-10-deficient C57Bl/6 mice raised under similar conditions seldom developed rectal prolapse. While injection of complete Freund's adjuvant (CFA) significantly reduced insulitis, it did not ameliorate colitis in IL-10-deficient NOD mice indicating differential regulation of organ-specific autoimmunity by CFA. Phenotypic characterization of IL-10-/- mice revealed a significant increase in splenic macrophage numbers in NOD but not on the B6 background. This was accompanied by a heightened systemic inflammatory cytokine response and mortality following in vivo challenge with a toll-like receptor 9 agonist, CpG-containing DNA.

AB - Interleukin (IL)-10 is a potent anti-inflammatory cytokine and ablation of IL-10 exacerbates Th1-type autoimmune diseases. Even though type 1 diabetes (T1D) in NOD mice is believed to be Th1-mediated, the incidence and severity of T1D is unaltered in IL-10-deficient NOD mice raised under pathogen-free conditions. We describe for the first time, the outcome of IL-10 deficiency on islet and other organ-specific autoimmunity in NOD mice raised in a conventional facility. IL-10-deficient NOD mice under such conditions were protected from spontaneous as well as cyclophosphamide-induced diabetes, but were susceptible to diabetes induced by adoptive transfer of splenocytes from spontaneously diabetic NOD mice. Whereas the incidence of rectal prolapse was very high in this NOD.IL-10-/- mouse colony, IL-10-deficient C57Bl/6 mice raised under similar conditions seldom developed rectal prolapse. While injection of complete Freund's adjuvant (CFA) significantly reduced insulitis, it did not ameliorate colitis in IL-10-deficient NOD mice indicating differential regulation of organ-specific autoimmunity by CFA. Phenotypic characterization of IL-10-/- mice revealed a significant increase in splenic macrophage numbers in NOD but not on the B6 background. This was accompanied by a heightened systemic inflammatory cytokine response and mortality following in vivo challenge with a toll-like receptor 9 agonist, CpG-containing DNA.

KW - Autoimmunity

KW - Colitis and rectal prolapse

KW - Cytokine

KW - Diabetes

KW - IL-10

KW - Knockout mice

KW - Non-obese diabetic mice

KW - Rodents

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=33744517332&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744517332&partnerID=8YFLogxK

U2 - 10.1016/j.cyto.2006.04.006

DO - 10.1016/j.cyto.2006.04.006

M3 - Article

C2 - 16740391

AN - SCOPUS:33744517332

VL - 34

SP - 85

EP - 95

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 1-2

ER -