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IL-35 mitigates murine acute graft-versus-host disease with retention of graft-versus-leukemia effects.
- Source :
-
Leukemia (08876924) . Apr2015, Vol. 29 Issue 4, p939-946. 8p. 6 Graphs. - Publication Year :
- 2015
-
Abstract
- IL-35 is a newly discovered inhibitory cytokine secreted by regulatory T cells (Tregs) and may have therapeutic potential in several inflammatory disorders. Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation and caused by donor T cells and inflammatory cytokines. The role of IL-35 in aGVHD is still unknown. Here we demonstrate that IL-35 overexpression suppresses CD4+ effector T-cell activation, leading to a reduction in alloreactive T-cell responses and aGVHD severity. It also leads to the expansion of CD4+Foxp3+ Tregs in the aGVHD target organs. Furthermore, IL-35 overexpression results in a selective decrease in the frequency of Th1 cells and an increase of IL-10-producing CD4+ T cells in aGVHD target tissues. Serum levels of TNF-α, IFN-γ, IL-6, IL-22 and IL-23 decrease and IL-10 increases in response to IL-35. Most importantly, IL-35 preserves graft-versus-leukemia effect. Finally, aGVHD grade 2-4 patients have decreased serum IL-35 levels comparing with time-matched patients with aGVHD grade 0-1. Our findings indicate that IL-35 has an important role in reducing aGVHD through promoting the expansion of Tregs and repressing Th1 responses, and should be investigated as the therapeutic strategy for aGVHD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 29
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 101987564
- Full Text :
- https://doi.org/10.1038/leu.2014.310