Analysis of mechanisms of DNase1L3 for the clearance of self-DNA in the pathogenesis of systemic lupus erythematosus

• Project/Area Number: 26893188
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyushu University
• Principal Investigator: MITOMA Hiroki 九州大学, 大学病院, 助教 (60467909)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: DNase / アポトーシス / 自己抗原 / 全身性エリテマトーデス

Outline of Final Research Achievements

Loss of function of deoxynuclease 1-like-3 (DNase1L3) causes the familial systemic lupus erythematosus, however the molecular mechanisms have not been clarified yet. Each of the fraction of white blood cells expressed DNase1L3 mRNA and plasmacytoid dendritic cells showed the highest expression among white blood cells. IL-4 induced a prominent induction of DNase1L3 expression in monocytes/macorphages. DNase1L3 protein mostly localized in the cytosol and was secreted into the cell culture medium. The secreted protein kept a function as a DNase. It is suggested that DNase1L3 degrades extracellular DNA released from dying cells in the inflamed tissue and keeps a tissue homeostasis.