Th17 immune responses contribute to the pathophysiology of aplastic anemia
- 18 November 2010
- journal article
- Published by American Society of Hematology in Blood
- Vol. 116 (20), 4175-4184
- https://doi.org/10.1182/blood-2010-01-266098
Abstract
T helper type 17 (Th17) cells have been characterized based on production of interleukin-17 (IL-17) and association with autoimmune diseases. We studied the role of Th17 cells in aplastic anemia (AA) by isolating Th17 cells from patients blood (n = 41) and bone marrow (BM) mononuclear cells (n = 7). The frequency and total number of CD3+CD4+IL-17–producing T cells were increased in AA patients at presentation compared with healthy controls (P = .0007 and .02, respectively) and correlated with disease activity. There was an inverse relationship between the numbers of Th17 cells and CD4+CD25highFoxP3+ regulatory T cells (Tregs) in the blood of AA patients. Concomitant with the classical Th1 response, we detected the presence of CD4+ and CD8+ IL-17-producing T cells in a mouse model of lymph node infusion–induced BM failure. Although anti–IL-17 treatment did not abrogate BM failure, early treatment with the anti–IL-17 antibody reduced the severity of BM failure with significantly higher platelet (P < .01) and total BM cell (P < .05) counts at day 10. Recipients that received anti-IL-17 treatment had significantly fewer Th1 cells (P < .01) and more Treg cells (P < .05) at day 10 after lymph node infusion. Th17 immune responses contribute to AA pathophysiology, especially at the early stage during disease progression.Keywords
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