کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3355318 | 1217164 | 2015 | 6 صفحه PDF | دانلود رایگان |
• Aire is expressed in peripheral lymphoid tissues but its role there is poorly known.
• Transfer of wild-type lymphocytes to lymphopenic Aire−/− recipients causes colitis.
• Wild-type T cells hyperproliferate in Aire−/− recipients.
• Transferred FoxP3+ Tregs proliferated less in Aire−/− recipients.
• The results indicate a new role for peripherally expressed Aire in the control of intestinal tolerance.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in Autoimmune regulator (Aire), a transcriptional regulator of negative selection in thymus. However, Aire is also expressed in periphery, but the full range of Aire's peripheral function is unknown. Here, we transferred lymphocytes from wildtype donors into lymphopenic recipients with or without functional Aire. Following cell proliferation thus took place in Aire-sufficient or deficient environment. The wildtype lymphocytes hyperproliferated and induced disease in lymphopenic Aire−/− but not in Aire+/+ recipients. The disease was characterized by diarrhea, inflammation, and colitis, and in some recipients pancreatitis, gastritis, and hepatitis was also found. Our results identify Aire as an important regulator of peripheral T cell homeostasis in gastrointestinal tissues. Given a suitable trigger the absence of peripheral Aire leads to dysregulated T cell proliferation and disease.
Journal: Immunology Letters - Volume 167, Issue 1, September 2015, Pages 17–22