Compromised central tolerance of ICA69 induces multiple organ autoimmunity.

摘要: For reasons not fully understood, patients with an organ-specific autoimmune disease have increased risks of developing responses against other organs/tissues. We identified ICA69, a known β-cell autoantigen in Type 1 diabetes, as potential common target multi-organ autoimmunity. NOD mice immunized ICA69 polypeptides exhibited exacerbated inflammation only the islets, but also salivary glands. To further investigate autoimmunity, two genetically modified mouse lines were generated to modulate thymic expression: heterozygous ICA69del/wt line and medullary epithelial cell-specific deletion Aire-ΔICA69 line. Suboptimal central negative selection ICA69-reactive T-cells was observed both lines. spontaneously developed coincident pancreas, glands, thyroid, stomach. Our findings establish direct link between compromised expression autoimmunity multiple ICA69-expressing organs, identify novel mechanism for development diseases.