All-trans-retinoic acid shifts Th1 towards Th2 cell differentiation by targeting NFAT1 signalling to ameliorate immune-mediated aplastic anaemia
- 1 December 2020
- journal article
- research article
- Published by Wiley in British Journal of Haematology
- Vol. 191 (5), 906-919
- https://doi.org/10.1111/bjh.16871
Abstract
Severe acquired aplastic anaemia (AA) is a serious disease characterised by autoreactive T cells attacking haematopoietic stem cells, leading to marrow hypoplasia and pancytopenia. Immunosuppressive therapy combined with antithymocyte globulin and ciclosporin can rescue most patients with AA. However, the relapse after ciclosporin withdrawal and the severe side effects of long-term ciclosporin administration remain unresolved. As such, new strategies should be developed to supplement current therapeutics and treat AA. In this study, the possibility of all-trans-retinoic acid (ATRA) as an alternative AA treatment was tested by using an immune-mediated mouse model of AA. Results revealed that ATRA inhibited T-cell proliferation, activation and effector function. It also restrained the Fas/Fasl pathway, shifted Th1 towards Th2 cell development, rebalanced T-cell subsets at a relatively high level and corrected the Th1/Th2 ratio by targeting NFAT1 signalling. In addition, ATRA inhibited Th17 cell differentiation and promoted regulatory T-cell development. Therefore, ATRA was an effective agent to improve AA treatment outcomes.Funding Information
- Muilticenter Clinical Research Project, Medical College of Jiaotong University (DLY201814)
- the Hospital-Public CrossLink Project of Shanghai Jiao Tong University (YG2017MS31)
- Innovation Program of Shanghai Municipal Education Commission (15ZZ052)
- The Science and Technology Commission of Pudong District, Shanghai Municipality (PKJ2015-Y04)
- The National Natural Science Foundation of China (81570121, 81870082, 81970114)
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