IL-10-deficiency unmasks unique immune system defects and reveals differential regulation of organ-specific autoimmunity in non-obese diabetic mice.
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.
Rajagopalan
Govindarajan
G
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA. rajag@mayo.edu
Kudva
Yogish C
YC
Sen
Moon M
MM
Marietta
Eric V
EV
Murali
Narayana
N
Nath
Karl
K
Moore
Jodi
J
David
Chella S
CS
D000818:Animals; D015551:Autoimmunity; D018899:CpG Islands; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D007107:Immune System / Q000473:pathology*; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000172:deficiency*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010641:Phenotype; D051193:Toll-Like Receptors / Q000378:metabolism
D051193:Toll-Like Receptors; D016753:Interleukin-10; D005620:Freund's Adjuvant