| First Author | Moritani M | Year | 1994 |
| Journal | Int Immunol | Volume | 6 |
| Issue | 12 | Pages | 1927-36 |
| PubMed ID | 7696210 | Mgi Jnum | J:25734 |
| Mgi Id | MGI:73434 | Doi | 10.1093/intimm/6.12.1927 |
| Citation | Moritani M, et al. (1994) Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes in non-obese diabetic mice. Int Immunol 6(12):1927-36 |
| abstractText | To study the paracrine effect of IL-10 on autoimmune insulitis and diabetes, we produced IL-10 transgenic non-obese diabetic (NOD) mice (NOD-IL-10) in which murine IL-10 was expressed in pancreatic islet A cells under the control of a rat glucagon promoter without directly manipulating pancreatic islet B cells. Among 11 founder mice, four of four males and three of seven females developed diabetes by 10 weeks of age. Histological analysis of six NOD-IL-10 revealed severe insulitis and prominent ductal proliferation. NOD-IL-10 also showed spotty lymphocytic infiltration in the lung and liver in four of six founder mice. The onset of diabetes in NOD-IL-10 was remarkably earlier than that of 14 weeks of age at the earliest in female non-transgenic NOD mice. When the NOD-IL-10 mouse was backcrossed to C57BL/6 mice, none of the resulting F1, B-N2 or B-N3 generation toward C57BL/6 mice showed diabetes even at 39 weeks of age, in spite of the presence of peri-insulitis and prominent ductal proliferation, while two of four mice of the N-N2 generation toward NOD mice showed early-onset diabetes. Thus, transgenic paracrine expression of IL-10 in situ in the NOD genetic background enhances autoimmune insulitis and diabetes in their onset and severity, ignoring gender difference. Because expression of IL-10 was detected by polymerase chain reaction in pancreatic islets of non-transgenic NOD mice after 5 weeks of age, IL-10 secreted in situ is regarded to enhance cell-mediated autoimmune diabetes, in spite of established in vitro anti-Th1 activity of IL-10. |
