| Co-Investigator(Kenkyū-buntansha) |
KUBOTA Mitsuru Hokkaido Univ., Hospital, physician, 医学部・歯学部附属病院, 医員
KOBAYASHI Ichiro Hokkaido Univ., Hospital, physician, 医学部・歯学部附属病院, 医員
KAWAMURA Nobuaki Hokkaido Univ., Hospital, Lec, 医学部・歯学部附属病院, 講師 (90301879)
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| Research Abstract |
Autoimmune enteropathy is a rare disease characterized by severe and refracrory diarrhea and the presence of circulating ants-enterocyte autoantibody. We have identified autoimmune enteropathy-related 75 kDa antigen (AIE-75) as a candidate autoantigen in the disease, which distributes to the brush border of both the small intestine and proximal renal tubulus. The distribution of AIE-75 is limited to the apical site of the villi, suggesting that the expression is regulated in cell cycle-or maturation-dependent manners. To approach this, we analyzed cis-element of the promotor region of AIIE-75 gene using luciferase assay, and found that -9 to -63 bases upstream of the transcription initiation site is involved in he negative regulation of the gene expression.
The specificity and sensitivity of anti-AJE-75 antibody in autoimmune enteropathy were confirmed in collaboration with other groups. Furthermore, we identified an actin-binding protein, villin, as another autoantigen related to the disease.
AIE-75 was found to be a responsible gene for Usher's syndrome type IC which is characterized by deafness and retinopathy. Indeed, AIE-75 was also expressed in both epithelial cells of the inner ear and retina. We found that ALE-75 is involved in the assembly of photoreceptor with cadherin 23 and myosin VII in the retina, but that the expression of AIE-75 is independent of the expression of the both proteins.
Some cases of autoimmune enteropathy are inherited in an X-linked manner, named immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) of which cause is the mutation of a forkhead winged helix transcription factor, FOXP3. We found a novel mutation of FOXP3, T1117G, in a mild case of IPEX.
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