Journal
LEUKEMIA
Volume 29, Issue 4, Pages 939-946Publisher
SPRINGERNATURE
DOI: 10.1038/leu.2014.310
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [91029703, 81102271, 81273268]
- Suzhou city [SS201032, SZS201109]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Province's Key Medical Center [ZX201102]
- Jiangsu Provincial Special Program of Medical Science [BL2012005]
- National clinical key subject construction project, National Public Health Grand Research Foundation [201202017]
- Jiangsu Provincial Innovative Research Team, Qing Lan project of Jiangsu Province, Program for Changjiang Scholars and Innovative Research Team in University [IRT1075]
- National Institutes of Health [R01 AI091977]
- NCI Comprehensive Cancer Center Support CORE grant [CA21765]
- ALSAC
Ask authors/readers for more resources
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-alpha, IFN-gamma, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available