Abstract:
:Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT), but the mechanisms leading to overload are unknown. Here, we determined iron levels and the expression of iron regulatory proteins in the liver and gut of nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice that underwent transplantation with syngeneic (histocompatible) or allogeneic (histoincompatible) T lymphocytes. Infusion of histoincompatible T cells resulted in a significant rise in serum iron levels and liver iron content. Iron deposition was accompanied by hepatocyte injury and intestinal villous damage. Feeding of low- or high-iron diet was associated with appropriate ferroportin 1 and hepcidin responses in mice given histocompatible T cells, whereas mice given histoincompatible T cells showed inappropriate up-regulation of duodenal ferroportin 1 and a loss of expression of hepatic hepcidin. These findings suggest that alloreactive T cell-dependent signals induced dysregulation of intestinal iron absorption, which contributed to liver iron overload after HCT.
journal_name
Bloodjournal_title
Bloodauthors
Bair S,Spaulding E,Parkkinen J,Shulman HM,Lesnikov V,Beauchamp M,Canonne-Hergaux F,Kowdley KV,Deeg HJdoi
10.1182/blood-2008-09-178517subject
Has Abstractpub_date
2009-02-19 00:00:00pages
1841-4issue
8eissn
0006-4971issn
1528-0020pii
blood-2008-09-178517journal_volume
113pub_type
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